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Immune Responses to Guided Imagery During Breast Cancer Treatment


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The use of relaxation and guided imagery to reduce stress and improve immune function has great potential benefits for patients with breast cancer. This pilot study used a pretest-posttest experimental design with 28 breast cancer patients, aged 25 to 75 years, with the diagnosis of stage 0, 1, or 2 breast cancer. The experimental group received a relaxation and guided imagery intervention and the control group received standard care. The effects of the intervention on immune function were measured by natural killer (NK) cell cytotoxicity and IL-2-activated NK cell activity prior to surgery and 4 weeks postsurgery. NK cell activity was measured using a 15-hr incubation chromium release assay. Cytotoxicity of NK cells was measured against chromium-labeled K-562 target cells. IL-2 was used to enhance reactivity of NK cells against tumor cells. After incubation for 15 hr, cytotoxicity was measured through the release of radioactive chromium. Significant differences between groups were found at 4 weeks postsurgery. T-tests showed increased NK cell cytotoxicity for the intervention group at 100:1, 50:1, and 25:1 effector cell: target cell ratios (E:T) (p < .01 to p < .05) and increased activation for IL-2 at 100:1, 50:1, 25:1, and 12.5:1 (E:T) (p < .01 to p < .05) for the intervention group as compared to the control group. These findings suggest that a relaxation intervention such as guided imagery could have an effect on NK cell cytotoxicity and NK cell cytotoxicity after activation with IL-2 in patients undergoing surgery for breast cancer.
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Biological Research For Nursing
The online version of this article can be found at:
DOI: 10.1177/1099800407309374
2008 9: 205Biol Res Nurs
Yang and Julie Djeu
Cecile A. Lengacher, Mary P. Bennett, Lois Gonzalez, Danielle Gilvary, Charles E. Cox, Alan Cantor, Paul B. Jacobsen, Chiu
Immune Responses to Guided Imagery During Breast Cancer Treatment
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Immune Responses to Guided Imagery
During Breast Cancer Treatment
Cecile A. Lengacher, RN, PhD, Mary P. Bennett, PhD, RN, ARNP,
Lois Gonzalez, PhD, ARNP, Danielle Gilvary, BS, Charles E. Cox, MD,
Alan Cantor, PhD, Paul B. Jacobsen, PhD, Chiu Yang, RN, MSN,
and Julie Djeu, PhD
Women, who are the most frequent users of com-
plementary alternative medicine (CAM), tend to seek
alternatives to help them cope with cancer diagnoses.
Lengacher and colleagues (2003) estimated that 64%
to 86% of women with breast cancer used CAM. Of
these women, 43% used relaxation techniques alone
at least once and 16% used them on a regular basis.
In addition, 27% used guided imagery at least once
with 6% using it regularly. Schmidt and Ernst (2004)
identified guided imagery as one of the most fre-
quently used CAM cancer therapies.
Psychological interventions and behavioral pro-
grams such as guided imagery and relaxation have
been shown to be effective in helping patients cope
with the stress of cancer. Although researchers have
studied the use of guided imagery in cancer patients,
orld cancer rates are expected to double by
2020. It is predicted that the number of per-
sons living with cancer will increase from 1.6
to 2.3 million from 2000 to 2050 (Simmonds, 2003). In
2006, an estimated 214,640 women in the United
States will be newly diagnosed with breast cancer, and
40,970 will die from the disease (Jemal et al., 2006).
Background: The use of relaxation and guided
imagery to reduce stress and improve immune func-
tion has great potential benefits for patients with
breast cancer. Methods: This pilot study used a
pretest–posttest experimental design with 28 breast
cancer patients, aged 25 to 75 years, with the diag-
nosis of stage 0, 1, or 2 breast cancer. The experi-
mental group received a relaxation and guided
imagery intervention and the control group received
standard care. The effects of the intervention on
immune function were measured by natural killer
(NK) cell cytotoxicity and IL-2–activated NK cell
activity prior to surgery and 4 weeks postsurgery. NK
cell activity was measured using a 15-hr incubation
chromium release assay. Cytotoxicity of NK cells
was measured against chromium-labeled K-562 tar-
get cells. IL-2 was used to enhance reactivity of NK
cells against tumor cells. After incubation for 15 hr,
cytotoxicity was measured through the release of
radioactive chromium. Results: Significant differences
between groups were found at 4 weeks postsurgery. T-
tests showed increased NK cell cytotoxicity for the inter-
vention group at 100:1, 50:1, and 25:1 effector cell:
target cell ratios (E:T) (p < .01 to p < .05) and increased
activation for IL-2 at 100:1, 50:1, 25:1, and 12.5:1 (E:T)
(p < .01 to p < .05) for the intervention group as com-
pared to the control group. Discussion: These findings
suggest that a relaxation intervention such as guided
imagery could have an effect on NK cell cytotoxicity
and NK cell cytotoxicity after activation with IL-2 in
patients undergoing surgery for breast cancer.
Keywords: guided imagery; immune response; breast
cancer; natural killer cells
From University of South Florida College of Nursing (CAL,
LG); Western Kentucky University School of Nursing
(MPB); H. Lee Moffitt Cancer Center, University of
South Florida (DG, CEC, AC, PBJ, JD); National Taiwan
University (CY).
Address correspondence to: Cecile A. Lengacher, University
of South Florida College of Nursing, 12901 Bruce B. Downs
Blvd, MDC 22, Tampa, FL 33612-4766; e-mail: clengach@
Biological Research Nursing
Volume 9 Number 3
January 2008 205-214
© 2008 Sage Publications
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few researchers have examined the effects of relax-
ation and guided imagery in randomized clinical tri-
als (Baider, Peretz, Hadani, & Koch, 2001; Burish,
Snyder, & Jenkins, 1991; Lyles, Burish, Krozely, &
Oldham, 1982; Syrjala, Donaldson, Davis, Kippes, &
Carr, 1995). Moreover, only a few studies have
examined the effects of relaxation and guided
imagery on the immune system in breast cancer
patients. Of these, only two were designed as ran-
domized clinical trials (Richardson et al., 1997; Yan,
Xinfan, Jigang, Hardy, & Mountainbear, 2001). In
addition, four nonrandomized studies examined the
effects of guided imagery without relaxation on
breast cancer patients’ immune systems (Bakke,
Purtzer, & Newton, 2002; Gruber et al., 1993;
Richardson et al., 1997; Schedlowski, Jung,
Schimanski, Tewes, & Schmoll, 1994).
Findings of these studies suggest that relaxation
and guided imagery, as self-regulating activities, can
influence the immune system by calming the corti-
cal and limbic regions of the brain (Bakke et al.,
2002; Richardson et al., 1997). The underlying
mechanism of action resides in the psychoneuroim-
mune network, a complex system of cells that inter-
act using extensive subcellular and molecular level
communication. This communication flows bidirec-
tionally among the neuroendocrine, nervous, and
immune systems (Booth, 1990; Glaser & Kiecolt-
Glaser, 2005).
Thus, in addition to alleviating feelings of anxi-
ety, it is possible that techniques such as relaxation
and guided imagery can improve the immune sys-
tem’s ability to fight cancer (Richardson et al.,
1997). Research has documented a relationship
between stress and changes in the immune system
(Andersen, Kiecolt-Glaser, & Glaser, 1994; Herbert
& Cohen, 1993; Kiecolt-Glaser, McGuire, Robles, &
Glaser, 2002; Kiecolt-Glaser, Robles, Heffner,
Loving, & Glaser, 2002; Mills & Dimsdale, 1996;
Morley, Benton, & Solomon, 1991). Stress-reducing
activities such as relaxation therapies may reduce
the effect of stress on glucocorticoids, which act as
immunomodulators (Reichlin, 1994; Spiegel &
Sephton, 2001). Various stressors act to downregu-
late the immune system, primarily through the
mechanism of elevated levels of cortisol, a glucocor-
ticoid. Cortisol is immunosuppressive and acts to
reduce the numbers and function of leucocytes as
well as to suppress natural killer (NK) cell activity
(Rabin, Cohen, Ganguli, Lysle, & Cunnick, 1989;
Whiteside, 2006; Zeller, McCain, & Swanson,
1996). Suppression of NK cell activity leads to a
decreased ability to resist illness, as NK cells play a
role in defense against many disease processes and
illnesses. However, suppression of NK cell activity
can be particularly damaging for persons with can-
cer, since NK cells have the ability to kill both virally
infected cells and tumor cells while sparing normal
cells (Kiecolt-Glaser, Robles, et al., 2002; Whiteside
& Herberman, 1995).
Decreased NK cell activity may, in fact, be an
important factor in the development of cancer (Adler,
Chervenick, Whiteside, Lotzova, & Herberman, 1988).
Low NK cell activity has been found in members of
cancer families as compared to age-matched individ-
uals without cancer (Bovbjerg & Valdimarsdottir,
1993; Shevde, Joshi, Shinde, & Nadkarni, 1998),
thus suggesting that unaffected family members may
be at higher risk for cancer. Recent evidence in ani-
mal models indicates that stress both decreases NK
cell activity and enhances metastasis of transplantable
tumors (Stefanski, 2001). NK cell activity may also
have some value in predicting recurrence, metastasis, and
decreased survival (Herberman, 1991; Levy, Herberman,
Maluish, Schlien, & Littman, 1985; Maes et al., 1998;
Whiteside, 2006; Whiteside & Herberman, 1995).
In addition to changing levels of glucocorticoids,
there are other ways of increasing or decreasing the
immune system response to pathogens and tumor
cells. Reichlin (1994) established the existence of a
link between the immune and neuroendocrine sys-
tems in the activation of immunocompetent cells,
which trigger cytokine release. These cytokines can
upregulate or downregulate the immune system’s
response to cellular invaders such as tumor cells.
Evidence indicates that immune competence and
cytokine activation are part of the normal process of
cancer prevention at the cellular level (Whiteside,
2006). This normal process may be hindered by
stress and the subsequent immunoresponse to stress
(Andersen et al., 1994). Cytokines have been reported
to play a key role in lymphocyte survival (Schluns &
Lefrancois, 2003). The cytokine interleukin-2 (IL-2)
has the most documented ability to enhance antitu-
mor activity (Van Parijs et al., 1999). A variety of
cytokines, particularly IL-2, are capable of modulat-
ing NK cells and act as potent stimulators of NK
cell cytotoxic function (Lanier, Benike, Phillips, &
Engleman, 1985; Trinchieri et al., 1984). IL-2
increases the cytotoxic capacity of NK cells by
increasing the expression of genes for the cytolytic
factors perforin and granzyme (DeBlaker-Hohe,
Yamauchi, Yu, Horvath-Arcidiacono, & Bloom,
1995; Lotzova, 1993; Salcedo, Azzoni, Wolf, &
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Perussia, 1993). Therefore, alterations in NK cell
cytotoxic function are regulated by changes in key
cytokines, and the effects of stress on these
cytokines ultimately leads to the changes in NK cell
functioning seen in stressed persons. Thus, it is the-
oretically possible that decreasing the effects of
stressors on cytokines will improve NK cell activity
and ultimately improve patients’ ability to resist the
progression of disease processes such as cancer.
Few clinical intervention studies have been con-
ducted to directly document the role of stress in the
development and progression of cancer. For instance,
it is highly unusual to have baseline stress and
immune measures on people prior to the diagnosis
of cancer, as most practitioners and diagnostic labo-
ratories do not include these measures in a standard
exam. Many of the measures used to document the
effects of stress on immune function and on the rel-
ative ability of a person’s immune cells to destroy
tumor cells are not readily available to practitioners
in a clinical setting. Therefore most people have
never had any type of cytotoxicity measure recorded
prior to being diagnosed with cancer. Furthermore,
recent research assessing the cytoxicity of NK cells
has been conducted primarily in animals and per-
sons who have never been diagnosed with cancer.
There have been several models designed to
determine how the immune system and tumor cells
interact in both humans and animals. Studies have
shown that decreased NK cell cytotoxicity is related
to increased metastasis (Levy, Herberman, Lippman,
& d’Angelo, 1987; Rakhmilevich, Janssen, Hao,
Sondel, & Yang, 2000). White, Jones, Cooke, and
Kirkham (1982) reported that women diagnosed
with breast cancer have significantly reduced NK
cell cytotoxicity (destruction of tumor cells). Also
there is a significant correlation between depressed
NK cell cytotoxicity and lymph node involvement in
women with primary breast cancer (Levy et al.,
1985). In contrast, increased NK cell activity leads
to cancer regression (Whiteside & Herberman,
1995), a finding that has significance for treatments
such as relaxation and guided imagery, which may
act to reduce the effects of stress and improve NK
cell functioning in cancer patients.
The purpose of the current study was to deter-
mine if relaxation and guided imagery had positive
effects on immunological functioning in early-stage
breast cancer patients. The premise for the study
was that there is a relationship among stress, cancer,
and immune activity; therefore, stress-reducing
interventions that have the potential to improve
immune activity also have the potential to improve
patients’ abilities to resist the actual disease process.
The use of relaxation and guided imagery in this
study relied on two assumptions:
Stress can affect the functioning of the immune
system, particularly NK cell cytotoxicity.
The progression of cancer is related to the reduc-
tion of immune surveillance by NK cells, known
to remove cancer cells (Bakke et al., 2002).
Sample and Design
This study was approved by the scientific review commit-
tee of the H. Lee Moffitt Cancer and Research Institute
and the University of South Florida Institutional Review
Board. Women who were diagnosed with early-stage
breast cancer but had not yet undergone surgery were
recruited from the breast cancer clinics at H. Lee
Moffitt Cancer Center and NCI Research Institute in
Tampa, Florida. Inclusion criteria included a diagno-
sis of early-stage breast cancer and the ability to read
and speak English.
An experimental randomized pretest–posttest
design was used to determine if there were differ-
ences in NK cell activity between women randomly
assigned to the control group receiving standard
care and those assigned to the intervention group.
Participants were enrolled during the clinic visit at
which they received their diagnosis, which was approx-
imately 2 to 3 weeks prior to surgery. Demographic
data were collected using a clinical history form,
which provided information on sociodemographics,
clinical history, and health-related behaviors such as
smoking, exercise, and caffeine and alcohol con-
sumption. Samples for the immunological assays, 30
ml of whole blood, were obtained at this time (base-
line) and 4 weeks postsurgery. To avoid possible vari-
ations because of differences in diurnal patterns, the
blood samples were collected at the same time in the
morning. Participants were randomly assigned to
either the control group or the experimental group.
Participants in both groups were invited to participate
in standard care planned for all patients through the
H. Lee Moffitt Cancer and Research Institute. In
addition, participants in the intervention group were
scheduled for a relaxation session as described below.
Participants in the control group received standard
Immune Responses to Guided Imagery / Lengacher et al. 207
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care and at the end of the intervention could receive the
relaxation tapes if they so desired. After 4 weeks, immuno-
logical data and clinical history data were obtained.
Participants in the intervention each met once for a
30-min relaxation and guided imagery session with a
therapist trained in relaxation guided imagery and also
received guided imagery tapes. They were asked to lis-
ten to the tapes a minimum of 3 times per week. In the
session, the therapist taught participants passive pro-
gressive relaxation to prepare them for guided imagery.
Training focused on concentration and visualization of
the immune cells destroying their cancer cells. This
method was originally described by Simonton,
Matthews-Simonton, and Creighton (1978) and has
been used in other studies (Bakke et al., 2002).
Prior to each relaxation session, the therapist–
nurse spent a few minutes talking with each patient
about how she was feeling physically and gave her
basic information on the immune system’s role in
combating cancer. The relaxation session began with
passive progressive relaxation, during which the thera-
pist suggested that patients relax a series of muscle
groups and body parts. The therapist explained that
passive progressive relaxation highlights deep breath-
ing techniques combined with imagery to create deep
relaxation and naturally calms the body and the mind,
preparing them for guided imagery. Patients were
encouraged to say a word silently to themselves, such
as relax, as they exhaled and mentally scanned the
muscle group for any further tension. Next, the thera-
pist asked patients to allow that tension to leave the
body and facilitated deeper relaxation by providing
imagery. Focused breathing was also incorporated into
the session (Berenson, 1988). Patients then moved into
guided imagery focused on health-promoting images. If
participants indicated they were having difficulty, the
therapist suggested soothing images. The women were
encouraged to use the audiotapes to practice at home
a minimum of 3 times per week and to document home
sessions in a daily diary.
Immune Parameters
The immune measures used in this study were NK cell
function and cytokine IL-2–enhanced NK cells (also
known as lymphokine activated killer cells or LAK).
These measures were selected as the most reliable and
most likely to demonstrate a change over time, based
on published studies of the susceptibility of NK cells
to psychoneural changes and the hypothesis that
NK-cell function may be modulated by behavioral
manipulation. These measures also allowed us to inves-
tigate the ability of IL-2 to activate NK cells, thus
demonstrating whether cellular products such as
cytokines also respond to the psychological intervention.
Preparation of Human Peripheral
Blood Mononuclear Cells (PBMC)
Prior to surgery and 4 weeks after surgery we obtained
30 ml of heparinized whole blood from each study
participant. Samples were diluted 1:2 in phosphate
buffer solution (PBS) and layered on 12 ml of Ficoll-
Hypaque solution (Gamero, Ussery, Reintgen, Puleo,
& Djeu, 1995). After centrifugation at 400g for 20
min at room temperature, the interface band of
PBMC was collected and washed twice with PBS.
The contaminating red blood cells were removed
from PBMC by hypotonic shock with sterile distilled
water for 30 s (Palma, Cassone, Serbousek, Pearson,
& Djeu, 1992). The PBMC were then resuspended in
RPMI-1640 medium containing 5% heat-inactivated
human AB serum (Biocell Laboratories, Carson, CA),
2 mM L-glutamine, 10 U/ml penicillin, 100 µg strep-
tomycin, and 5 mM/L HEPES buffer (GIBCO). All
media and reagents contained less than 0.1 ng/ml of
endotoxin, as determined by the Limulus Amoebocyte
Lysate assay (M. A. Biologics, Walkersville, MD), to
avoid nonspecific activation of the PBMC.
Measurement of Cytotoxicity
A 15-h chromium (
Cr) release assay was used to
measure the cytotoxicity of PBMC against K562
tumor cell targets (Nenlife Sciences; Rossi, Pericle,
Rashleigh, Janiec, & Djeu, 1994). Briefly, 96-well
rounded-bottom microliter plates were set up in trip-
licate wells with 100 ul of PBMC at various concen-
trations to achieve effector cell:target cell (E:T) ratios
of 100:1, 50:1, 25:1, and 12.5:1. Recombinant
human IL-2, 1000 units/ml, was added to PBMC.
The cells were then incubated at 37°C in 5% CO
2 hr. K562, an erythroleukemia NK sensitive tumor
cell line, was labeled with 100 µCi of Na
(Amersham, Arlington Heights, IL) for 1 hr at 37°C.
The cells were washed twice with PBS and 100 µl
were added to effector cells at 5 × 103 cells/well. After
a 15-hr incubation at 37°C, 100 µl of supernatant was
collected, and radioactivity of the
Cr released from
target cells was measured by a gamma counter. Samples
were collected in triplicate wells, and the mean value
was determined for each sample dilution: that is, 100:1,
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50:1, 25:1, and 12.5:1. The statistical program cor-
rected for outliers in the sample. The percentage of
specific lysis was calculated by the formula [Experimental
cpm-spontaneous release cpm/maximal release cpm
incorporated] x 100.
Antitumor activity may depend on concurrent
stimulation of T cells and macrophages that produce
cytokines, such as IL-2, which subsequently
increase the activity of other immune system com-
ponents. The tumoricidal activity of NK cells is
increased by cytokines. These activated NK cells are
also known as LAK cells and may respond differently
than NK cells to a similar stimulus. In this study, we
did not isolate NK cells from the PBMC population.
Instead, we used IL-2 to target activation of the NK
cells. LAK cells within the PBMC population were
produced by exposing some of the patients’ NK cells to
IL-2 during the 15-hr incubation period. Cytotoxicity
was then measured through the release of radioac-
tive chromium into the supernatant. Percentage
lysis was calculated at the 100:1, 50:1, 25:1, and
12.5:1 E:T ratios.
Statistical Analysis
Means generated from the independent groups—
relaxation and guided imagery compared to standard
care—were analyzed using pooled Student t tests.
Comparisons of differences within groups were made
with two-sided, paired t tests. ANCOVA was used to
determine if the two groups varied in immune func-
tion, adjusted for the covariates of age, stage of dis-
ease, and type of surgery. All statistical analyses were
conducted using SPSS statistical software.
We recruited 32 participants who met the inclusion
criteria, and 28 completed both pre- and poststudy
blood draws for the immunological assays, resulting
in an 88% completion rate. Through random assign-
ment, 13 were placed in the control group receiving
standard care, and 15 were placed in the guided
imagery group. Demographic and clinical character-
istics of the participants are provided in Table 1. The
majority (53%) were married, and a large percentage
(35.7%) were divorced. Although other ongoing
treatments for cancer could affect immune function,
we controlled for this possibility by ensuring that
there were no changes in these treatments during
the pretest to 4 weeks postsurgery study period,
which is the time period during which other medical
treatment for breast cancer usually begins. The
groups did not differ significantly on stage
of disease or type of surgery at baseline using
chi square analysis.
Imagery Practice
Women in the guided imagery group were asked to
listen to the tapes a minimum of 3 times per week.
All 15 women used the tapes to practice the guided
imagery; however, the amount of practice varied
from 0 to 16 times per week. Only 2 women
reported not practicing at all for 4 weeks. The over-
all mean number of practice sessions per week was
4.9, with the average number of weekly sessions for
each woman ranging from 2.3 to 13.6.
Immunological Studies
This study evaluated the functional NK cell cytotox-
icity measured by % lysis and LAK activity at four dif-
ferent E:T ratios. Data collected prior to surgery were
compared to data collected 4 weeks after surgery for
participants in both the intervention group and the
control group. As expected, at pretest there were no
significant between-group differences in NK cell
cytotoxicity (p > .05) or in LAK activity, indicating
that the random group assignment was reasonably
effective in controlling for possible differences in
baseline immune function (see Table 2).
At the 4-week posttest data-collection point,
two-tailed independent t tests indicated that func-
tional NK cell cytotoxicity (measured in % lysis) dif-
fered significantly between the intervention group
and the control group at E:T ratios of 100:1, 50:1,
and 25:1 (t tests, p < .01 to p < .05; Figure 1 and
Table 3). Also there were significant differences in
cytotoxicity from the IL-2–enhanced LAK cells for
participants between the two groups at E:T ratios of
100:1, 50:1, 25:1, and 12.5:1 (p < .01 to p < .05), as
shown in Figure 2. These results indicate that NK
cells from participants in the intervention group
were better able to respond to IL-2 stimulation than
NK cells from participants in the control group.
Functional cytotoxicity increased significantly for
women in the intervention group from pre- to
posttest (Figure 3). Although LAK activity decreased
for participants in both groups, most likely because
of the stress of surgery, it decreased significantly less
for those in the intervention group (Figure 4). This
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result indicates that the intervention was able to
buffer or mediate the effects of this stress on LAK
function. Analysis of covariance revealed no signifi-
cant differences in immune status between groups
due to covariates of age, stage of disease, or type of
surgery (p = .98 to p = .34).
This study tested the immunological effects of a 4-
week guided imagery program in 28 women with
stage 0, 1, or 2 breast cancer. The results show that
short-term relaxation and guided imagery had bene-
ficial immunological effects on NK cell cytotoxicity
and IL-2 activation of NK cells, or LAK activity, after
4 weeks of participation.
These findings support the earlier work of Gruber
and colleagues (1993) and Bakke, Purtzer, and
Newton (2002). Gruber’s group found that relaxation,
guided imagery, and biofeedback training were able to
increase NK cell activity in their sample. Bakke and
colleagues did not find significant increases in NK
210 Biological Research for Nursing/ Vol. 9, No. 3, January 2008
Table 1. Demographic and Clinical Characteristics of Study Population (N = 28)
Combined Experimental Group Control Group
Characteristic (N = 28) (n = 15) (n = 13)
Age (mean years) 52.6 48.3 57.6
Working status
Not working 10 (35.7) 6 (40.0) 4 (30.8)
Working full time 14 (50.0) 7 (46.7) 7 (53.9)
Working part time 3 (10.7) 1 (6.7) 2 (15.4)
Other 1 (3.6) 1 (6.7) 0
Level of education
High school diploma 8 (28.6) 1 (6.7) 7 (53.9)
Some college 15 (53.6) 10 (66.7) 5 (38.5)
Graduate education 5 (17.9) 4 (26.7) 1 (7.7)
Married 15 (53.6) 8 (53.3) 7 (53.9)
Not married category 13 (46.4) 7 (46.7) 6 (46.2)
Caucasian 26 (92.9) 14 (93.3) 12 (92.3)
Other 2 (7.1) 1 (6.7) 1 (7.7)
Cancer stage
0 7 (25.0) 5 (33.3) 2 (15.4)
1 16 (57.1) 7 (46.7) 9 (69.2)
2 5 (17.9) 3 (20.0) 2 (15.4)
Surgery type
Mastectomy 12 (42.9) 7 (53.9) 5 (33.3)
Lumpectomy 16 (57.1) 8 (53.3) 8 (61.5)
NOTE: Data are presented as n (%) unless otherwise noted.
Table 2. Independent t-test Comparison of Pretest NK Cell and IL-2 (LAK) Cytotoxicity
Control Group Intervention Group
(n = 13) (n = 15)
E:T Ratio Mean (SD) Mean (SD) Tp
NK 100:1 28.2 (14.2) 29.5 (12.1) –.27 .788
NK 50:1 18.7 (10.0) 23.1 (12.4) –1.01 .326
NK 25:1 11.8 (6.6) 15.2 (10.1) –1.04 .307
NK 12.5:1 7.0 (6.1) 9.4 (7.5) –.89 .378
IL-2 100:1 31.5 (12.6) 37.3 (13.5) –1.15 .259
IL-2 50:1 22.9 (9.6) 30.0 (12.5) –1.65 .109
IL-2 25:1 16.0 (8.6) 20.5 (9.0) –1.36 .185
IL-2 12.5:1 10.6 (5.4) 15.2 (8.6) –1.64 .111
NOTE: LAK = lymphokine activated killer cells; E:T ratio = the ratio of effector cell to target cell. Target cells were K562 tumor cells.
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Immune Responses to Guided Imagery / Lengacher et al. 211
100:1 50:1 25:1
E:T Ra
p = .001
p = .001
p = .001 p = .017
% Lysis
Postintervention IL-2 (LAK)
Figure 2. Between-group comparison of lymphokine-
activated killer cell (LAK) activity (IL-2–stimulated NK cells) at
4 weeks posttest.
100:1 50:1 25:1 12.5:1
ET Ratio
% Lysis
Pre- and Posttest Data—NK,
Cr Difference
Figure 3. Changes from baseline measures in NK cell cyto-
toxicity by group. NK cytotoxicity decreased in the control group
while remaining stable or improving in the intervention group.
100:1 50:1 25:1 12.5:1
ET Ratio
% Lysis
Pre- and Posttest Data—IL2 Difference
Figure 4. Changes from baseline in lymphokine-activated killer
cell (LAK) cytotoxicity by group. LAK activity decreased in both
groups but demonstrated less decrease in the intervention group.
Table 3. Independent t-test Comparison of Posttest NK Cell and IL-2 (LAK) Cytotoxicity
Control Group Intervention Group
(n = 13) (n = 15)
E:T Ratio Mean (SD) Mean (SD) Tp
NK 100:1 20.3 (9.7) 33.7 (11.3) –3.33 .003
NK 50:1 15.4 (7.7) 25.7 (10.6) –2.88 .008
NK 25:1 10.9 (6.5) 17.7 (8.4) –2.37 .025
NK 12.5:1 6.5 (5.6) 10.1 (6.9) –1.44 .160
IL-2 100:1 21.6 (12.2) 38.2 (12.1) –3.59 .001
IL-2 50:1 14.8 (9.7) 29.5 (10.5) –3.82 .001
IL-2 25:1 9.0 (6.9) 19.7 (7.7) –3.74 .001
IL-2 12.5:1 6.8 (5.7) 12.7 (6.3) –2.55 .017
NOTE: LAK = lymphokine activated killer cells; E:T ratio = the ratio of effector cell to target cell. Target cells were K562 tumor cells.
100:1 50:1 25:1
% Lysis
Control Relaxation
p = .160p = .025p = .008p = .003
Postintervention NK,
Cr Cytotoxicity
Figure 1. Between-group comparison of NK cytotoxicity
(measured in % lysis) at 4 weeks posttest.
at UNIV OF SOUTH FLORIDA on February 8, 2013brn.sagepub.comDownloaded from
cell activity but instead reported increased numbers
of NK cells in persons treated with relaxation ther-
apy. Because the current study did not include raw
counts of NK cells, it cannot be determined if relax-
ation increased actual numbers of cells or just
increased the cancer-killing abilities of the NK cells
already present.
However, not all studies in this area have had sim-
ilar results. Richardson and colleagues (1997)
reported an increase in interferon gamma in persons
in the imagery/relaxation group with no accompany-
ing increase in NK cell cytotoxicity and a paradoxical
decrease in neopterin, a substance that is normally
increased when macrophages are stimulated with
interferon gamma. Given that two out of the three
findings in this study were contrary to what would
normally be predicted, it is difficult to say how these
findings fit into the current models of immune system
function. In a similar study, Larson and colleagues
(2000) reported no changes in NK cell activity after a
two-session guided imagery intervention in presurgi-
cal breast cancer patients despite the fact that inter-
feron gamma decreased significantly in the control
group but remained stable in the intervention group.
Again, this result is somewhat contrary to current the-
ory concerning the actions of interferon gamma on
NK cell activity, but it may be that two sessions were
insufficient to create a measurable change.
The immune effects of relaxation and guided
imagery may be explained by the release of potent fac-
tors such as neuropeptides and cytokines that can mod-
ulate the immune response (Ben-Eliyahu, Shakhar,
Page, Stefanski, & Shakhar, 2000). In the current sam-
ple of patients, NK cell cytotoxicity was enhanced in the
intervention group, and LAK activity showed resilience
to stress-induced immunosuppression. According to the
current understanding of the actions of IL-2 and other
cytokines such as interferon gamma, these cytokines
act to stimulate and enhance NK cell cytotoxicity, turn-
ing regular NK cells into LAK cells. IL-2 enhancement
occurs because IL-2 is an 18-kDa protein capable of
increasing cytotoxic function through induction of the
expression of genes for cytolitic factors perforin and
granzyme (DeBlaker-Hohe et al., 1995; Lotzova,
1993). This ability may be one of the underlying
mechanisms for the significant increase in NK cell
activity and stablility of LAK activity demonstrated in
the relaxation group.
Questions have arisen concerning the detection of
changes in immune responses when a participant is
already in a stressed condition, because this stress may
lead to low NK cell activity prior to any intervention and
may interfere with the actions of the intervention on
immune function (Schulz & Schulz, 1992). For women
in this study, stress-related immunosuppression may
have been a factor in all of the women because of their
recent cancer diagnoses. However, randomization ade-
quately controlled for this potential, as demonstrated by
the fact that there were no significant between-group
differences in NK cell functioning at baseline. In addi-
tion, the possible confounding factor of differing reac-
tions to the stress of chemotherapy was avoided by
conducting the intervention and posttest sampling prior
to the patients’ chemotherapy treatment phase.
In conclusion, this study supports the hypothesis
that a presurgical relaxation and guided imagery inter-
vention can improve immune function in women
undergoing surgical treatment for breast cancer. This
study also contributes to the growing body of literature
concerning the mechanisms by which stress reduction
techniques may enhance immune function and sup-
ports the use of relaxation and guided imagery in
breast cancer patients as a complementary therapy.
This study was funded by the American Cancer Society,
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... The protocol for the meta-analysis was developed in accordance with the PICOS approach. Studies were included in this analysis if they met the following criteria: [36] N N N N N N High Reich et al (2014) [13] N N N N N N High Robins et al (2013) [37] N N N N N N High Lengacher et al (2008) [12] N N N N N N High Baker et al (2012) [17] N N N N N N High Cho et al (2011) [38] N N N N N N High Cohen et al (2011) [20] N N N N N N High Eremin et al (2009) [39] N N N N N N High Antoni et al (2009) [31] N N N N N N High McGregor et al (2009) [15] N N N N N N High Ross et al (2009) [16] N N N N N N High Lengacher et al (2008) [ [18] N N NC N N N Moderate Lekander et al (1997) [23] N N N N N N High Zhou et al (2017) [40] N N N N N N High Shen et al (2017) [35] N N NC N N N Moderate Dong et al (2016) [41] N N NC N N N Moderate Li et al (2016) [42] N NC N N N N High Ren et al (2015) [43] N NC NC N N N Moderate Peng et al (2015) [44] N NC NC N N N Moderate Zheng et al (2015) [45] N N NC N N N Moderate Guo et al (2015) [46] N N NC N N N Moderate Chen et al (2013) [47] N NC NC N N N Moderate Han et al (2013) [48] N N NC N N N Moderate Zheng et al (2015) [45] N NC N N N N High Wang et al (2002) [22] N NC The complete details about our study protocol are provided in the About pages at PROSPERO. ...
... However, the degree of cancer patient participation, compliance, and individual stress levels influences its efficacy; moreover, none of the studies that focused on SM took this point into consideration, and SM intervention showed no significant psychological effect as compared to control analogues. [12,13] To the best of our knowledge, the effect of PI on the immune response may be associated with improvements in psychological emotions, hypothalamicpituitary-adrenal axis (HPA axis), and the sympathetic nervous system. The reason for the nonsignificant immune effect of SM might be the ineffective nature of the PI or low level of emotion distress. ...
... Lengacher et al showed that compared to T cells, NK cells were more susceptible to suppression during cancer treatment. [12] However, studies still indicate that PI can result in changes in the levels of some immune indicators in cancer patients during different treatment periods. [12,13,15,17,20] Wang et al have shown that NK cell activity is associated with the severity of anxiety and depression in cancer patients and that the degree of psychological recovery might affect NK cell activi-ty. ...
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Objective: To determine whether psychological intervention (PI) changes the levels of immune indicators in cancer patients. Methods: We conducted a systematic search published up to July 2018, followed by a manual search. Randomized controlled trials were included. Two reviewers independently screened and extracted data, which were analyzed using Review manager 5.3. Results: Twenty-nine studies were included including four kinds of PI. Only stress management didn't result in immune changes; only cognitive behavior therapy affect NK cell activity. PI did not change immune indicators on cancer patients who completed therapy. Compared to patients not receiving PI, those received PI had significantly higher NK cell count and activity in whole blood; and serum levels of IL-2, IL-4, IFN-γ, lgA, and lgG. However, the differences in the serum levels of IL-6, IL-10, TNF-α, and IgM were not significant (P > .05), and the changes recorded for the CD3, CD4, and CD8 cell count, and CD4/CD8 ratios were inconsistent. Conclusions: Although there are considerable evidences of PI's immune effect, but its magnitude was moderate. Therefore, it may be premature to conclude whether PI affects immunity of cancer patients. Further research is warranted, with special focus on the PI types and treatment methods.
... In 29 studies (38.7%), healthy volunteers were included as the study population [34,. Other samples included patients or vulnerable adults, e.g., patients with various types of cancer [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82], patients with HIV infection [35,[83][84][85][86][87], patients with rheumatoid arthritis [26,[88][89][90], older adults [91][92][93][94], patients with asthma/allergies [95][96][97], widows/women who had lost a close relative to cancer [98,99], patients with ulcerative colitis [100,101], women with depression after bypass surgery [102], patients with late-life insomnia [103], women suffering from infertility [104], veterans [105], and patients who had undergone surgery [106]. The mean age of the participants varied between 18.5 and 78.8 years. ...
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Background: There is consistent evidence showing an interplay between psychological processes and immune function in health and disease processes. Objectives: The present systematic review and meta-analysis aims to provide a concise overview of the effectiveness of stress-reducing psychological interventions on the activation of immune responses in both healthy subjects and patients. Methods: Included are 3 types of challenges: in vivo, in vitro, and psychophysiological. Such challenges are designed to mimic naturally occurring immune-related threats. Results: A systematic literature search was conducted using PubMed, EMBASE, and PsychInfo, resulting in 75 eligible studies. The risk of bias was assessed with the Cochrane risk-of-bias tool. Across all studies, a small-to-medium effect size was found for the effects of psychological interventions on optimization of the immune function (g = 0.33; 95% CI 0.22-0.43). While the largest effects were found for in vivo immune-related challenges (g = 0.61; 95% CI 0.34-0.88; especially on studies that incorporated skin tests and wound healing), studies incorporating psychophysiological challenges and in vitro immune-related stimulations similarly suggest more optimal immune responses among those receiving stress-reducing interventions (g = 0.28; 95% CI 0.15-0.42). Conclusion: These findings showed substantial heterogeneity depending on the type of challenge, the study populations, and the intervention types. These data demonstrate support for the effectiveness of stress-reducing psychological interventions in improving immunity in studies that tested immune function by means of incorporating an in vivo,in vitro, or psychophysiological challenge. Future research should more consistently incorporate challenges into the study design to gather more insights in the mechanisms underlying the optimized immune function following a psychological intervention. This is also relevant for clinical practice, as psychological interventions can possibly supplement, or at least partially replace, current drug treatments in various somatic conditions to reduce side effects.
... Growing evidence suggests that psychosocial interventions improve QOL in cancer survivors. [1] Among the efficacious approaches, interventions emphasizing guided imagery have been associated with improved QOL, reduced treatment-related side effects, and improved immune function in cancer survivors [2][3][4] though not all studies have found this association. [5] A single arm pretest/posttest study using the present imagery-based intervention indicated that 30 post-treatment breast cancer survivors living in rural Alaska experienced increased post-treatment general and breast cancer-specific QOL, improved spiritual well-being, and decreased distress. ...
... Growing evidence suggests that psychosocial interventions improve QOL in cancer survivors. [1] Among the efficacious approaches, interventions emphasizing guided imagery have been associated with improved QOL, reduced treatment-related side effects, and improved immune function in cancer survivors [2][3][4] though not all studies have found this association. [5] A single arm pretest/posttest study using the present imagery-based intervention indicated that 30 post-treatment breast cancer survivors living in rural Alaska experienced increased post-treatment general and breast cancer-specific QOL, improved spiritual well-being, and decreased distress. ...
... The pooled results showed that, adjuvant psychological interventions were more effective in improving natural killer cell cytotoxicity than treatment as usual or being on a waiting list (ES=-3.99).The pre-post-ES for natural killer cell cytotoxicity was also statistically significant (ES=-2.53). Statistically significant improvements in natural killer cell cytotoxicity were report in three studies [28][29][30].Despite statistical nosignificant in the Lindemalm and colleague's studies, all point estimates were in favor of psychological interventions, which suggests that psychological interventions have significant effect on improving natural killer cell cytotoxicity of breast cancer patients. ...
... Similar to RVT, guided imagery utilizes progressive relaxation of muscle groups combined with focused breathing techniques intended to calm the mind and prepare it for guided imagery. 74 Guided imagery is a consciousness-focused practice intended to increase awareness with a relaxed, open mind for the purpose of confronting a specific concern or issue. Guided imagery is viewed as a way to allow patients to participate in their own healing and has been reportedly used for healing, symptom management, promotion of positive health behaviors, and making positive life changes. ...
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Objective This is a review of spiritually based interventions (eg, mindfulness-based stress reduction) that utilized psychoneuroimmunological (PNI) outcome measures in breast cancer survivors. Specifically, this review sought to examine the evidence regarding relationships between spiritually based interventions, psychosocial-spiritual outcomes, and biomarker outcomes in breast cancer survivors. Methods A systematic search of 9 online databases was conducted for articles of original research, peer-reviewed, randomized and nonrandomized control trials from 2005–2015. Data were extracted in order to answer selected questions regarding relationships between psychosocial-spiritual and physiological measures utilized in spiritually based interventions. Implications for future spiritually based interventions in breast cancer survivorship are discussed. Results Twenty-two articles were reviewed. Cortisol was the most common PNI biomarker outcome studied. Compared with control groups, intervention groups demonstrated positive mental health outcomes and improved or stable neuroendocrine-immune profiles, although limitations exist. Design methods have improved with regard to increased use of comparison groups compared with previous reviews. There are few spiritually based interventions that specifically measure religious or spiritual constructs. Similarly, there are few existing studies that utilize standardized religious or spiritual measures with PNI outcome measures. Findings suggest that a body of knowledge now exists in support of interventions with mindfulness-breathing-stretching components; furthermore, these interventions appear to offer potential improvement or stabilization of neuroendocrine-immune activity in breast cancer survivors compared to control groups. Conclusion From a PNI perspective, future spiritually based interventions should include standardized measures of religiousness and spirituality in order to understand relationships between and among religiousness, spirituality, and neuroendocrine-immune outcomes. Future research should now focus on determining the minimum dose and duration needed to improve or stabilize neuroendocrine-immune function, as well as diverse setting needs, including home-based practice for survivors who are too ill to travel to group sessions or lack economic resources.
Integrative oncology, as it is implemented in most National Cancer Institute-designated comprehensive cancer centers, refers to the practice of utilizing complementary health modalities in conjunction with conventional medicine. The following chapter will introduce the evidence behind the most utilized forms of integrative oncology and their role in supportive cancer care. This overview aims to familiarize practitioners with the theoretical framework and clinical utility of common complementary modalities, such as acupuncture, yoga, mind-body therapies, as well as nutritional and herbal supplement use in the cancer setting.
Stress associated with diabetes makes managing diabetes harder. We investigated whether mindfulness-based stress reduction (MBSR) could reduce diabetes distress and improve management. We recruited 38 participants to complete an MBSR program. Surveys and lab values were completed at baseline and post-intervention. Participants showed significant improvement in diabetes-related distress (Cohen's d -.71, p < .002), psychosocial self-efficacy (Cohen's d .80, p < .001), and glucose control (Cohen's d -.79, p < .001). Significant improvements in depression, anxiety, stress, coping, self-compassion, and social support were also found. These results suggest that MBSR may offer an effective method for helping people better self-manage their diabetes and improve mental health.
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Background: In a review and meta-analysis conducted in 1993, psychological preparation was found to be beneficial for a range of outcome variables including pain, behavioural recovery, length of stay and negative affect. Since this review, more detailed bibliographic searching has become possible, additional studies testing psychological preparation for surgery have been completed and hospital procedures have changed. The present review examines whether psychological preparation (procedural information, sensory information, cognitive intervention, relaxation, hypnosis and emotion-focused intervention) has impact on the outcomes of postoperative pain, behavioural recovery, length of stay and negative affect. Objectives: To review the effects of psychological preparation on postoperative outcomes in adults undergoing elective surgery under general anaesthetic. Search methods: We searched the Cochrane Register of Controlled Trials (CENTRAL 2014, Issue 5), MEDLINE (OVID SP) (1950 to May 2014), EMBASE (OVID SP) (1982 to May 2014), PsycINFO (OVID SP) (1982 to May 2014), CINAHL (EBESCOhost) (1980 to May 2014), Dissertation Abstracts (to May 2014) and Web of Science (1946 to May 2014). We searched reference lists of relevant studies and contacted authors to identify unpublished studies. We reran the searches in July 2015 and placed the 38 studies of interest in the `awaiting classification' section of this review. Selection criteria: We included randomized controlled trials of adult participants (aged 16 or older) undergoing elective surgery under general anaesthesia. We excluded studies focusing on patient groups with clinically diagnosed psychological morbidity. We did not limit the search by language or publication status. We included studies testing a preoperative psychological intervention that included at least one of these seven techniques: procedural information; sensory information; behavioural instruction; cognitive intervention; relaxation techniques; hypnosis; emotion-focused intervention. We included studies that examined any one of our postoperative outcome measures (pain, behavioural recovery, length of stay, negative affect) within one month post-surgery. Data collection and analysis: One author checked titles and abstracts to exclude obviously irrelevant studies. We obtained full reports of apparently relevant studies; two authors fully screened these. Two authors independently extracted data and resolved discrepancies by discussion.Where possible we used random-effects meta-analyses to combine the results from individual studies. For length of stay we pooled mean differences. For pain and negative affect we used a standardized effect size (the standardized mean difference (SMD), or Hedges' g) to combine data from different outcome measures. If data were not available in a form suitable for meta-analysis we performed a narrative review. Main results: Searches identified 5116 unique papers; we retrieved 827 for full screening. In this review, we included 105 studies from 115 papers, in which 10,302 participants were randomized. Mainly as a result of updating the search in July 2015, 38 papers are awaiting classification. Sixty-one of the 105 studies measured the outcome pain, 14 behavioural recovery, 58 length of stay and 49 negative affect. Participants underwent a wide range of surgical procedures, and a range of psychological components were used in interventions, frequently in combination. In the 105 studies, appropriate data were provided for the meta-analysis of 38 studies measuring the outcome postoperative pain (2713 participants), 36 for length of stay (3313 participants) and 31 for negative affect (2496 participants). We narratively reviewed the remaining studies (including the 14 studies with 1441 participants addressing behavioural recovery). When pooling the results for all types of intervention there was low quality evidence that psychological preparation techniques were associated with lower postoperative pain (SMD -0.20, 95% confidence interval (CI) -0.35 to -0.06), length of stay (mean difference -0.52 days, 95% CI -0.82 to -0.22) and negative affect (SMD -0.35, 95% CI -0.54 to -0.16) compared with controls. Results tended to be similar for all categories of intervention, although there was no evidence that behavioural instruction reduced the outcome pain. However, caution must be exercised when interpreting the results because of heterogeneity in the types of surgery, interventions and outcomes. Narratively reviewed evidence for the outcome behavioural recovery provided very low quality evidence that psychological preparation, in particular behavioural instruction, may have potential to improve behavioural recovery outcomes, but no clear conclusions could be reached.Generally, the evidence suffered from poor reporting, meaning that few studies could be classified as having low risk of bias. Overall,we rated the quality of evidence for each outcome as 'low' because of the high level of heterogeneity in meta-analysed studies and the unclear risk of bias. In addition, for the outcome behavioural recovery, too few studies used robust measures and reported suitable data for meta-analysis, so we rated the quality of evidence as `very low'. Authors' conclusions: The evidence suggested that psychological preparation may be beneficial for the outcomes postoperative pain, behavioural recovery, negative affect and length of stay, and is unlikely to be harmful. However, at present, the strength of evidence is insufficient to reach firm conclusions on the role of psychological preparation for surgery. Further analyses are needed to explore the heterogeneity in the data, to identify more specifically when intervention techniques are of benefit. As the current evidence quality is low or very low, there is a need for well-conducted and clearly reported research.
When we really feel unwell, we should seek the advice of a good and scientifically trained doctor. The doctor will examine us, and, if suspicious of a serious illness, we will be requested to undergo various examinations. The tests may finally tell that we have cancer. What to do next? This may seem a silly question, but today in many societies the patient does have choices and the patient’s life rests on what he or she does with this right to choose. What the individual finally decides to do will be his or her prerogative, but we should hope for a well-informed decision. In this decision-making process it is always possible to make mistakes. The problem with cancer is that by the time the patient realises that he/she got it wrong it may be too late. This was the case of Steve Jobs, the founder of the computer company Apple, who was diagnosed with pancreatic cancer but decided to delay conventional therapy in order to pursue other kinds of therapies such as acupuncture, herbal therapy, diet therapy and spiritual exercises. After 9 months of exclusive non-conventional therapies he decided to undergo chemotherapy and surgery, but it was too late. Does Job’s story prove that complementary psychological therapies (CPTs), such as spiritual exercises and meditation, are therefore useless? Not really. In fact, CPTs do have an important role to play in the overall plan to tackle the challenges of cancer, but such a role should be seen as synergistic with that of conventional therapies (surgery, chemotherapy, radiotherapy), especially when a cancer has been already diagnosed. In addition, CPTs can be useful in the prevention of cancer by decreasing the levels of stress, apart from their use as adjuvant therapies throughout the period of conventional treatment. During remission, CPTs may provide some aid in preventing cancer recurrence or at least help individuals to be mentally better prepared to absorb the shock of recurrence of cancer if it does happen.
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We believe that any questions regarding whether the CNS can alter immune system functions no longer remain. It can conclusively be stated that the immune system is susceptible to influences of the CNS. It remains to be determined whether all classes of lymphocytes, NK cells, macrophages, polymorphonuclear leukocytes, and other antigen-processing cells are all susceptible to CNS influences. We have presented evidence that peripheral blood lymphocytes may not reflect the immunological activity of lymphocytes within lymphatic tissue after being influenced by a stressor. Thus, all types of immunological cells must be evaluated in different organs. Whether the immune system of young and old animals respond in the same way must also be determined. The sex of the animal needs to be taken into consideration. What immune responses are important to measure? Do in vitro responses reflect the ability of an animal to resist infectious disease or susceptibility to autoimmune and malignant diseases? Certainly, absence of an immune response is detrimental to health. It must be determined whether moderately suppressed immune function in multiple compartments is as detrimental as total absence of an immune response in a single immunological compartment. The data that we have presented with respect to adjuvant arthritis indicate that an immune response in the peripheral of the animal can be modified by a stressor and influence an immunopathological process. This may indicate that the most important immune compartment to evaluate with respect to altering disease susceptibility is the peripheral blood and that lymphoid tissue may be interesting, but not clinically relevant. The reasons why the peripheral blood and lymphoid tissue differ in their immunological function following exposure to a stressor must be determined. We have reviewed information indicating that lymphoid tissue is innervated and that such innervation can modify immune function. In addition, hormones released by the CNS may alter immune function. Yet, much of this data are contradictory and whether immune enhancement or suppression occurs is not clearly defined with respect to any experimental manipulation involving denervation or the addition of hormones to in vitro cultures. Whether this reflects the age of the experimental animal, the type of immune response being measured, the adequacy of the experimental procedure, background rearing conditions of the animals, the amount of noise in the animal room, the diet of the animals, or the number of animals housed per cage all remain to be determined. Our purpose has not been to provide a comprehensive review of all of the data relating to the immune system/CNS interaction.(ABSTRACT TRUNCATED AT 400 WORDS)
Neuroblastoma is the most common extracranial, solid tumor in children. Despite intensive chemotherapy and bone marrow transplantation, the 5- year projected survival rate is 20% to 25%. In vitro studies have shown enhanced natural killer cell (NK) lysis of tumor cells after exposure of NK cells to interleukin-2 (IL-2). In vivo studies have demonstrated similar immunologic effects but have also revealed severe toxicities associated with the use of IL-2. IL-12 is a newly described cytokine that has several properties, including the ability to act synergistically with IL-2 in generating lymphokine-activated killer cells (LAK) against known tumor targets. We investigated the role of IL- 12 in the generation of peripheral blood mononuclear cell (PBMC) lysis of neuroblastoma cell lines. PBMC were activated with IL-12 alone and in combination with IL-2. Whereas IL-12 alone produced only modest enhancement of NK cell cytotoxicity, the combination of IL-2 and IL-12 was most effective in activating NK cell lysis of neuroblastoma cell lines. Further, we showed that large granular lymphocytes were the effector cells involved in target cell lysis. Finally, the CD18 molecule was shown to be critical in the lysis of neuroblastoma cells by activated PBMC.
The feasibility of in vitro interleukin 2 (IL-2) activation and expansion of mononuclear cells (MNCs) derived from adult patients with acute myelogenous leukemia (ANLL) was studied. Patients' natural killer (NK) and lymphokine-activated killer (LAK) cell activity was compared with that of normal donors in terms of: (a) cytolytic activity (four- hour 51Cr release assay) against an NK-sensitive target (K562), NK- resistant targets (Raji/Daudi), and fresh/cryopreserved autologous and allogeneic leukemic blasts; (b) proliferation and expansion in culture with 1,000 U/mL recombinant IL 2 (rIL 2); and (c) the cell surface phenotype of the cultured cells. In 21 of 24 patients with active disease (AP) MNCs derived from the peripheral blood (PBL) or bone marrow (BM) could be cultured and expanded in the presence of rIL 2. These cultures initially contained between 30% and 50% blasts, and during 2 to 4 weeks of culture destruction of blasts and enrichment of up to 60% in cells with the morphology of large granular lymphocytes (LGLs) was observed. Expansion in culture varied between two- and 100- fold. MNCs from all patients in remission (RP) could be activated by rIL 2 and expanded up to 30-fold after 1 to 3 weeks in culture. NK activity of fresh PBLs from AP was significantly lower than in normal controls, whereas NK activity of RP was within the normal range. High levels of postactivation NK and LAK activity on K562/Raji/Daudi and on fresh/cryopreserved leukemic blasts was generated in approximately 50% of cases of AP and in most RP. Cell surface phenotype studies showed that cultured cells derived from ANLL patients were significantly enriched (up to 40%) in NKH-1 (Leu 19) positive cells, with RP LAK cells also expressing a high proportion of CD16 positive cells (up to 40%). This study has shown that it is feasible to activate and significantly expand killer cells derived from active disease and remission ANLL patients during 1 to 3 weeks culture with IL 2 with good maintenance of cytolytic activity. Both initial NK activity and LAK generation was optimal in remission patients. Based on data from this study, a clinical protocol has been developed for treatment of early relapse ANLL patients with LAK cells cultured for 1 to 3 weeks and systemic IL 2.
This report summarizes data from social confrontations studies in laboratory rats dealing with the effects of psychosocial stress on immune functioning and tumor metastasis. The paper focuses on the physiological alterations observed in subdominant males after 2 days of continuous social confrontation. A significant loss of body mass and elevated plasma concentrations of adrenal hormones in subdominant males indicate a stressful social environment. Subdominant males showed lower numbers of blood CD4 and CD8 T cells as well as reduced activity levels of T cells and natural killer (NK) cells relative to control subjects. In order to evaluate the possible health impact of suppressed NK functioning, we used the MADB 106 tumor model. A 10-fold lower tumor clearance in subdominant males demonstrates suppression of the animals' capacity to prevent metastatic development. The relationship between individual behavior and immunological outcome is briefly discussed. Together, the study of male rats in social confrontations appears to be a good model to investigate stress-induced immune modulation and tumor metastasis under relatively naturalistic social conditions.
provide an overview of current knowledge on the role of opioid peptides as immunomodulators review the effects of opioid peptides in vitro and then discuss the emerging evidence that opioid peptides acutely modulate natural killer (NK) cell activity in humans in vivo effects of morphine treatment on the immune system in animals will then be addressed the possible role of the immune system in the development of opiate addiction will be discussed (PsycINFO Database Record (c) 2012 APA, all rights reserved)
In order to evaluate the effects of a behavioral intervention on endocrine and immunological parameters, 24 breast cancer patients were investigated after standard surgical treatment of their tumors and without adjuvant tumor treatment. Of these, 14 patients were allocated to the intervention group and 10 patients served as controls. Interventions were conducted once a week over a period of 10 weeks. To determine short- and longer-term intervention effects on plasma concentration of cortisol and lymphocyte numbers, blood samples were taken before and after the second and 10th session. Psychological variables such as illness-related coping showed no changes within the intervention period (10 weeks). However, there were short- (pre- versus post sessions) and longer-term (9 weeks) reductions in plasma levels of cortisol in the intervention group. In parallel to the reduced plasma concentration of cortisol, a short-term increase of lymphocyte numbers after the second and the 10th session, as well as an increase over a period of nine weeks in the intervention group, was observed. This data indicate that behavioral intervention influences endocrine and immunological functions in breast cancer patients.
Psychoneuroimmunological stress- and intervention studies are summarized and discussed especially with respect to the immunological parameters used. A description is given of the studies on bereavement, on examinations, and on the effects of various psychosocial situations and on experimental manipulations on immunological parameters as well as of intervention studies. Following an analysis of the immunological parameters regarding their susceptibility to psychosocial changes, a model for research in the field of psychoneuroimmunology is presented. This overview reveals that the results of the reviewed studies prove to be inconsistent. Cell counts and mitogen assays are the most frequently used parameters, while NKCA and specific anti-viral antibodies against latent viruses give the clearest results. When interpreting results of psychoneuroimmunological studies it should be considered that for most of the parameters the pathophysiological relevance is not yet established. A model which connects interrelations between psychosocial conditions, immunological parameters and disease outcome can be useful to categorize and evaluate existing and future studies and also can prevent misleading conclusions. Derived from this model recommendations for future research will be discussed.
That the inheritance of mutations in tumor susceptibility genes alone cannot determine risk for developing cancer is now well accepted. Immune functions have long been recognized as one of the important risk modifying factors in this regard. In an attempt to develop a multiparametric approach to identify high risk individuals from cancer families, we have examined NK cell function in unaffected members from familial breast cancer families. We have also carried out a parallel study of T lymphocyte functions in these individuals. Our studies demonstrate a significantly lower NK cell activity in members from cancer families. T lymphocyte activity also showed a similar trend, with the unaffected members demonstrating a notably lowered T lymphocyte function. In addition the data from patients reveals differential sensitivity of NK and T lymphocyte function to the disease phenotype. Implications of these observations are discussed.