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ABSTRACT: Interleukin-12 (IL-12) and related cytokines induce activation and differentiation of T cells. Our aim was to investigate the associations between genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial disease.
The final study population consisted of 100 women with Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.
We found that the IL12B SNP rs3212227 was associated with both susceptibility and severity of TFI. The minor allele C was rare and only one CC homozygote was found among the controls. AC heterozygotes were more common among TFI cases than among controls (P = 0.009) and were associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06-5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52).
The results suggest that variation in the IL12B gene partly explains inter-individual differences in disease susceptibility and severity.
Human Reproduction 05/2012; 27(7):2217-23. · 4.47 Impact Factor
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ABSTRACT: Vitamin D deficiency during the fetal period or infancy is one of the suggested environmental factors for type 1 diabetes and for its increasing incidence. To test this hypothesis we compared serum 25-hydroxyvitamin D (25(OH)D) levels during early pregnancy in mothers of children who subsequently developed type 1 diabetes (case mothers) with mothers of non-diabetic healthy children (control mothers) of the same age.
Children with type 1 diabetes were identified from the nationwide prescription register. 25(OH)D concentration was measured from serum samples collected during the first trimester of pregnancy from all Finnish women (Finnish Maternity Cohort). A total of 343 case mothers and 343 control mothers were included in the study. Samples were collected throughout the year. Samples from case and control mothers were matched on the day of collection.
Mean 25(OH)D levels in case mothers (43.9 nmol/l) and control mothers (43.7 nmol/l) were not different. Of all mothers, 481 (70.1%) were vitamin D-deficient or -insufficient.
No difference was found in serum 25(OH)D concentrations during first trimester of pregnancy between mothers whose children later on developed type 1 diabetes, and mothers of non-diabetic ' healthy' children of the same age. It is difficult to detect possible effects of mothers' vitamin D deficiency during early pregnancy on the development of type 1 diabetes in the offspring in this population, as such a large proportion of mothers were vitamin D-deficient or -insufficient.
Diabetologia 01/2012; 55(5):1291-4. · 6.81 Impact Factor
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R Rimpiläinen,
N Hautala,
Jk Koskenkari,
J Rimpiläinen,
Pp Ohtonen,
P Mustonen, H-M Surcel,
E-R Savolainen,
M Mosorin,
Ti Ala-Kokko,
T Juvonen
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ABSTRACT: Minimized cardiopulmonary bypass (MCPB) circuits have been shown to reduce cerebral and retinal microembolisation during coronary artery bypass graft (CABG) surgery compared to conventional CPB (CCPB) circuits. Our aim was to evaluate whether the reduction of microembolisation is sustained in aortic valve surgery, as well as to evaluate the effects of MCPB on inflammatory, endothelial, and platelet activation markers.
Patients were randomized to undergo aortic valve replacement (AVR), with or without CABG, with MPCB (n=20) or CCPB (n=20). After anaesthesia induction and termination of CPB, standardized digital retinal fluorescein angiography images were obtained on both eyes and analyzed in a blinded fashion. Blood samples were collected at eight time points until the third postoperative day.
Fewer patients in the MCPB group showed evidence of microembolic perfusion defects on postperfusion retinal fluorescein angiographs compared to the CCPB group (37% vs. 63%, absolute difference 26%, 95% CI -5% -51%, P = 0.194). Polymorphonuclear leukocyte (PMN) elastase and von Willebrand factor release were statistically significantly reduced in the MCPB group, but there were no significant differences in other markers of inflammation, coagulation or endothelial activation. A significantly higher three-fold increase in the amount of shed blood was collected to the cell saver with a higher rate of intraoperative platelet transfusion in the MCPB group compared to CCPB.
The use of MCPB was associated statistically insignificantly with less retinal microemboli compared to CCPB. MCPB was complicated by excess bleeding and need for transfusion. The feasibility of MCPB techniques in valve surgery requires further studies.
Perfusion 07/2011; 26(6):479-86. · 0.92 Impact Factor
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S Heliövaara-Peippo,
R Oksjoki,
K Halmesmäki,
R Kaaja,
J Teperi,
S Grenman,
A Kivelä, H-M Surcel,
E Tomas,
M Tuppurainen,
R Hurskainen,
J Paavonen
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ABSTRACT: To compare, whether women with menorrhagia, treated with either hysterectomy or LNG-IUS, differ in their cardiovascular risk profile during 10-year follow-up.
A total of 236 women were randomized to treatment by hysterectomy (n=117) or LNG-IUS (n=119). Their cardiovascular risk factors were analyzed at baseline, at 5 years, and at 10 years. As 55 originally randomized to the LNG-IUS group had hysterectomy during the follow-up, all analyzes were performed by actual treatment modality.
Waist circumference, body-mass index (BMI), blood pressure, and the levels of blood lipids, serum high-sensitivity CRP (hsCRP) and tumor necrosis factor alpha (TNF-α) were measured, and the use of medication for hypertension, diabetes, hypercholesterolemia, and ischemic heart disease was analyzed.
After 5 years, an increase in the use of diabetes medication during the follow-up was only detected in the hysterectomy group (from 1.7% to 6.7%, P=0.008 vs from 5.1% to 8.4%, P=0.08), as well as they had significantly higher serum levels of TNF-α (108.59 pg/ml vs 49.02 pg/ml, P=0.001) and hsCRP (1.55 μg/ml vs 0.78 μg/ml, P=0.038) at 5- and 10-years. There was no difference between the groups in the use of cardiovascular medication, neither was there difference in blood pressure, waist circumference, BMI, or concentrations of blood lipids.
Hysterectomy seems to be associated with increased levels of serum inflammatory markers and increased diabetes medication, which in turn, may predispose individual to future cardiovascular events.
Maturitas 06/2011; 69(4):354-8. · 2.77 Impact Factor
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ABSTRACT: Chlamydia trachomatis-induced fallopian tube damage leading to tubal factor infertility (TFI) is linked with TNF, IL-10, and probably IFNG gene polymorphisms. The aim of this study was to clarify the contribution of these cytokine gene polymorphisms to interindividual variation in C trachomatis-specific immune responses and the cross-regulation of secreted cytokines and single nucleotide polymorphisms (SNPs). Cytokine polymorphisms (IL-10 -1082A/G, -819T/C, and -592A/C, IFNG +874T/A, and TNF -308G/A) were genotyped by polymerase chain reaction in 139 women. C trachomatis-specific immune responses were measured using lymphocyte proliferation (LP) induced by C trachomatis E and F strains and chlamydial heat shock protein 60 antigens. Cytokine secretion was measured in culture supernatants of infected and uninfected mononuclear leukocytes. IL-10 -1082/-819/-592 and IFNG +874 SNPs were associated with the intensity of LP responses to C trachomatis antigens. These cytokines also interact with each other and a cumulative effect of IL-10 -1082 and IFNG +874 genotypes was seen in LP responses to C trachomatis antigens. Our data suggest that interleukin-10 and interferon-γ regulate C trachomatis-specific immune responses in humans and that genetic variation in the expression of their coding genes explains interindividual variation in host immune responses to C trachomatis infection.
Human immunology 03/2011; 72(3):278-82. · 2.55 Impact Factor
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ABSTRACT: Evidence suggests that inflammation may be associated with increased risk of ovarian cancer but there is paucity of studies investigating this association, especially using over-time changes in inflammatory biomarkers.
We conducted a prospective population-based case-control study nested within the Finnish Maternity Cohort (FMC). Within the FMC, 170 women with ovarian cancer who had donated serum samples to the cohort twice, ≥1 year apart, before cancer diagnoses were identified. One control per case was matched for age, parity and sampling date.
Comparing the highest with lowest tertiles, the odds ratio (OR) of ovarian cancer using the first set of serum samples (mean lag time to cancer diagnosis 9.0 years) was 1.62 [95% confidence interval (CI) 0.93-2.83]. However, analysis conducted using the second set of serum samples donated closer to cancer diagnosis (mean lag time 6.4 years) revealed a significantly increased risk of ovarian cancer comparing extreme tertiles of C-reactive protein (CRP) concentrations; OR 1.96 (95% CI 1.11-3.4). Over time, increases in individuals' CRP concentrations were also associated with increased risk; OR 1.90 (95% CI 1.12-3.23).
The results suggest that inflammation may precede ovarian cancer since increasing CRP concentrations, both across tertiles and longitudinally at the individual level, were associated with increased risk.
Annals of Oncology 02/2011; 22(8):1916-21. · 6.43 Impact Factor
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W Wang,
F R Stassen, H-M Surcel,
H Ohman,
A Tiitinen,
J Paavonen,
H J C de Vries,
R Heijmans,
J Pleijster,
S A Morré,
S Ouburg
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ABSTRACT: Susceptibility to Chlamydia trachomatis infections is 40% host based. microRNA-146a is a negative regulator of Tolllike receptor (TLR) signaling and possesses functional polymorphisms which decrease the production of premiR-146a and mature miR-146a. Single nucleotide polymorphisms (SNPs) in NLRP3 are associated with decreased NLRP3 expression and hypoproduction of interleukin (IL)-1beta. We investigated whether the SNPs miR-146a G>C (rs2910164), NLRP3 C>T (rs4925663) and G>A (rs12065526) are associated with the susceptibility to and severity of C. trachomatis infection. The genotypes of three SNPs were tested in two cohorts: cohort 1 consists of Dutch women (n = 318) attending a sexually transmitted disease (STD) clinic and cohort 2 (n = 277) consists of subfertile (n = 184) and healthy Finnish women (n=93). While in cohort 1 the analyzed SNPs were not associated with the susceptibility to C. trachomatis infections (C. trachomatis-positive vs. C. trachomatis-negative), we showed in C. trachomatis-positive women that the NLRP3 mutant AG and AA genotypes were a risk factor for the development of symptoms (P = 0.047, OR = 2.9) and more specifically for having lower abdominal pain (genotype AA: P = 0.022, OR = 31.3). In the Finnish tubal pathology group versus the control group no statistical significant differences in the incidences of the SNPs studied were found, nor for the degree of tubal pathology. In conclusion, the mutant NLRP3 A allele is a risk factor for the development of symptoms, specifically lower abdominal pain, after a C. trachomatis infection in women attending an STD clinic.
Drugs of today (Barcelona, Spain: 1998) 11/2009; 45 Suppl B:95-103. · 1.28 Impact Factor
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ABSTRACT: Chronic inflammation induced by Chlamydia trachomatis can lead to tubal factor infertility (TFI). To investigate the genetic basis of chlamydial TFI and various manifestations of tubal damage, we studied functional polymorphisms in selected cytokine genes (IL-10 -1082 A/G, -819 T/C, and -592 A/C; IFN-gamma +874 T/A; TNF-alpha -308 G/A; TGF-beta1 codons 10 T/C and 25 G/C; and IL-6 -174 G/C) in 114 women with laparoscopically verified TFI (hereafter known as "cases") and in 176 controls. Evidence of past infection with C. trachomatis was demonstrated in 96 cases by use of a combined test for humoral and cell-mediated immune responses to chlamydial elementary bodies (EBs) and chlamydial heat-shock protein 60 antigens. We found that the IL-10 -1082 AA genotype and the TNF-alpha -308 A allele increased the risk of severe tubal damage in women with infertility associated with C. trachomatis (odds ratio [OR], 7.3 [95% confidence interval {CI}, 1.3-42] and 4.0 [95% CI, 1.0-16], respectively), suggesting that differences in these genes contribute to the wide spectrum of disease manifestations.
The Journal of Infectious Diseases 06/2009; 199(9):1353-9. · 6.41 Impact Factor
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ABSTRACT: Placental abruption may be a manifestation of acute and chronic inflammatory process. We wanted to assess the association of first-trimester serum C-reactive protein (CRP), Chlamydia pneumoniae antibodies, Chlamydia trachomatis antibodies or chlamydial heat-shock protein 60 (CHSP60) antibodies to placental abruption.
Retrospective case-control study.
University Hospital.
A total of 181 women with subsequent placental abruption and 261 control women with normal pregnancy.
Serum samples collected at first trimester (mean 10.4 gestational weeks) were analysed for CRP levels, C. pneumoniae-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies and C. trachomatis-specific IgG, IgA and CHSP60 antibodies.
Placental abruption.
The levels of CRP showed no difference between the cases and the controls (median 2.35 mg/l [interquartile range {IQR} 1.09-5.93] versus 2.28 mg/l [IQR 0.92-5.01], not significant). C. pneumoniae-specific IgG and IgA as well as C. trachomatis-specific IgG, IgA and CHSP60 antibody frequencies were similar between the groups. There was no association between CRP levels and chlamydial antibodies.
These markers of inflammation in early pregnancy failed to predict subsequent placental abruption.
BJOG An International Journal of Obstetrics & Gynaecology 04/2008; 115(4):486-91. · 3.41 Impact Factor
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ABSTRACT: To study Chlamydia trachomatis seroprevalence trends and geographical distribution over time in Finland.
First pregnancy serum samples were retrieved from the Finnish Maternity Cohort serum bank for the subcohort of 8000 women stratified by calendar years (1983-1989, 1990-1996, 1997-2003) and age at time of sample withdrawal (14-22 and 23-28 years). C trachomatis antibodies were determined using standard major outer membrane protein peptide ELISA. The spatiotemporal variation of C trachomatis seroprevalence rates was visualised by a series of maps.
A decreasing C trachomatis seroprevalence trend from 1983 to 2003 was seen for both women under 23 years of age (20.8% to 10.6%) and 23-28-year-old women (19.1% to 12.5%). Constant clusters were seen around the largest cities and in eastern Finland although seroprevalence rates were generally decreasing throughout the country.
Only a few population-based serological studies have been undertaken on C trachomatis epidemiology over time. In Finland the seroprevalence of C trachomatis is decreasing all over the country, albeit with small clusters remaining.
Sexually transmitted infections 03/2008; 84(1):19-22. · 2.18 Impact Factor
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A Rainio,
N Hautala,
O Pelkonen,
T Palosaari,
J Heikkinen,
M Mosorin,
J Lahtinen,
P Taskinen,
V Anttila, H M Surcel,
M Lepojärvi,
T Juvonen,
F Biancari
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ABSTRACT: In order to investigate the neuroprotective efficacy of off-pump coronary artery bypass surgery (OPCAB) over conventional on-pump coronary artery bypass surgery (CCAB), we have performed a prospective randomized study evaluating retinal circulation changes after OPCAB and CCAB.
Twenty patients were randomized to OPCAB or CCAB. Retinal fluorescein angiography and 60 degrees black-and-white as well as color fundus photographs of both eyes of each patient were taken 1 to 24 h before and 5 to 6 days after the operation.
Patients undergoing OPCAB had more severely stenosed carotid arteries (P=0.075), higher incidence of slightly diseased ascending aorta (P=0.087) and higher Northern New England Cardiovascular Study Group stroke risk score (P=0.075). Neither stroke nor transient ischemic attack occurred postoperatively in these patients. Inferotemporal retinal arterial embolization and microinfarction was detected in one patient after CCAB, but in none of the OPCAB group.
The risk of retinal embolism can be minimized by the use of OPCAB and, most likely, by adequate epiaortic ultrasound scanning of the ascending aorta and avoiding clamping in case of severely diseased aorta.
The Journal of cardiovascular surgery 01/2008; 48(6):773-9. · 1.56 Impact Factor
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ABSTRACT: The administration of insulin has been shown to exert cardioprotective and immunomodulatory properties. Ischemia and inflammation are typical features of acute coronary syndrome, thus it was hypothesized that high-dose glucose-insulin-potassium (GIK) treatment could suppress the systemic inflammatory reaction and attenuate myocardial ischemia-reperfusion injury in patients with unstable angina pectoris after urgent coronary artery bypass surgery.
Forty patients with unstable angina pectoris scheduled for urgent coronary artery bypass surgery and cardiopulmonary bypass were randomly assigned to receive either high-dose insulin treatment (short-acting insulin 1 IU/kg/h with 30% glucose 1.5 ml/kg/h administered separately) or control treatment (saline). Blood glucose levels were targeted to 6.0-8.0 mmol/l in both groups by adjusting the rate of glucose infusion in the GIK group and by additional insulin in the control group as needed.
High-dose insulin treatment was associated with significantly lower average C-reactive protein (23.8 vs. 40.1 mg/l, P= 0.008) and free fatty acid levels (0.22 vs. 0.41 mmol/l, P= < 0.001) post-operatively. Average blood glucose levels were comparable during the intensive care unit (ICU) stay (7.1 vs. 6.9 mmol/l, P= 0.5) and 95% of the control patients received supplemental insulin. The pro-inflammatory cytokine response [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha)] did not differ between the groups and beneficial effects on myocardial injury were not detected.
High-dose insulin treatment has potential anti-inflammatory properties independent of its ability to lower blood glucose levels. Even profound suppression of free fatty acid levels, the attenuation of myocardial ischemia-reperfusion injury was not detected.
Acta Anaesthesiologica Scandinavica 09/2006; 50(8):962-9. · 2.19 Impact Factor
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ABSTRACT: To evaluate the role of Chlamydia trachomatis-induced humoral and cell-mediated immune (CMI) responses in predicting tubal factor infertility (TFI).
Blood samples were taken from 88 women with TFI and 163 control women. C. trachomatis and chlamydial heat shock protein 60 (CHSP60)-specific immunoglobulin G (IgG) antibodies were analysed using enzyme-linked immunosorbent assay (ELISA) kits. Proliferative reactivity of peripheral blood mononuclear cells was studied in vitro against Chlamydia elementary body (EB) and recombinant CHSP60 antigens.
C. trachomatis-specific IgG antibodies were found more frequently (43.2 versus 13.5%), and the antibody levels were higher in the TFI cases than in the controls (P < 0.001). C. trachomatis EB-induced lymphocyte responses were positive in 81.8% of the TFI cases and 58.9% of the controls (P < 0.001). Similarly, CHSP60-induced lymphocyte responses were found in 45.5% of the TFI cases and 30.7% of the controls (P < 0.001). CHSP60 antibody test was the best single test predicting TFI. Compared to cases with all four markers negative, the estimated risk for TFI was 4.1 (95% CI 1.4-11.9) among those with one positive marker and 19.9 (95% CI 6.9-57.4) among those with three to four positive markers.
Our results show that TFI prediction model can be improved by combining tests for humoral and CMI response to chlamydial antigens.
Human Reproduction 07/2006; 21(6):1533-8. · 4.47 Impact Factor
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ABSTRACT: Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genetic background. To study a relationship between interleukin-10 (IL-10) promoter -1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-gamma responses were found in subjects with IL-10 -1082 GG genotype when compared to those with -1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects with a history of noncomplicated and complicated infection is needed to further understand the confounding factors associated with the development of C trachomatis associated sequelae.
Genes and Immunity 05/2006; 7(3):243-9. · 3.87 Impact Factor
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ABSTRACT: Surgical stress and general anaesthesia suppress immune functions, including natural killer cell (NK) activity. This suppression could be attributed, at least in part, to the effect of opiates.
Twenty patients undergoing abdominal hysterectomy received epidural sufentanil (50 microg) either before (pre-emptive) or at the end (control group) of surgery. Post-operative pain relief was provided using sufentanil from a patient-controlled epidural analgesia (PCEA) system. Systemic immunity was assessed by determining leucocyte counts, NK cell counts and activity, lymphocyte response to mitogen stimulation, and secretion of pro-inflammatory cytokines.
In the pre-emptive group there was a significant decrease in NK activity on the first and third post-operative day (P < 0.05) compared with baseline values and on the third postoperative day (P < 0.05) compared with the control group. The number of total leucocytes and neutrophiles increased in both groups post-operatively, but no differences were found in the levels of mononuclear lymphocyte populations or in their mitogen responses. Interleukin-6 (IL-6) concentration increased in both groups after the operation. In addition, at the end of the surgery the IL-6 level was greater in the control group than in the pre-emptive group. Interleukin-1 (IL-1) levels had decreased significantly at the end of surgery and 4 h later compared with baseline levels in the pre-emptive, but not in the control group.
Pre-emptive epidural sufentanil during combined propofol and isoflurane anaesthesia had minor effects on the immune response after hysterectomy. The lower production of pro-inflammatory cytokines (IL-1, IL-6) in the pre-emptive group compared with the control group is beneficial, but its clinical importance remains to be determined.
Acta Anaesthesiologica Scandinavica 07/2004; 48(6):750-5. · 2.19 Impact Factor
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ABSTRACT: Chlamydia trachomatis-associated tubal factor infertility (TFI) involves enhanced humoral and cell-mediated immune response to the chlamydial 60 kDa heat shock protein (CHSP60). We evaluated the role of CHSP60-induced immune response in TFI by studying lymphocyte proliferation and cytokine (interferon (IFN)-gamma, interleukin (IL)-12 and IL-10) secretion in response to C. trachomatis elementary body (EB) and CHSP60 antigens in 57 women with TFI and in 76 women with other causes of infertility. Positive proliferative response of PBMC to CHSP60 was more common in the TFI group (20/57; 36%) than in the other groups (17/76; 22%) although the frequency or the median responses did not differ significantly (1.6, range 0.2-22.1 versus 1.4; 0.2-24.4). C. trachomatis EB induced significantly higher IFN-gamma and lower IL-10 secretion in the TFI group compared to the other groups. The EB and CHSP60 induced IL-12 secretion was similar in all study groups and correlated with IFN-gamma secretion in the other but not in the TFI group. The lack of correlation between EB-induced IL-12 and IFN-gamma production and simultaneously found prominent IL-10 secretion in response to CHSP60 in the TFI group suggests that the CHSP60 may have a specific role in regulating the immune reactions during chlamydial infection and may consequently contribute to the immunopathogenesis of TFI.
Clinical & Experimental Immunology 03/2003; 131(2):299-303. · 3.36 Impact Factor
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ABSTRACT: The relationship between Chlamydia trachomatis tubal factor infertility (TFI) and the host's immunoregulatory genes was studied.
Cell-mediated immune responses to C. trachomatis and chlamydial heat shock protein (CHSP60) were determined by lymphocyte proliferation assay. HLA-DQ alleles and interleukin-10 (IL-10) promoter polymorphism (-1082 A/G) were analysed in 52 TFI cases and in 61 controls by PCR.
HLA-DQB1 or DQA1 alleles did not significantly differ between the TFI group and the control group. However, DQA1*0102 and DQB1*0602 alleles together with IL-10 -1082AA genotype were found significantly more frequently in the TFI patients than in the controls (0.18 and 0.02 respectively; P = 0.005). Five (22%) of the 23 patients who had a positive lymphocyte proliferative response to CHSP60 were positive also for IL-10 -1082AA and for the HLA-DQA1*0102 and HLA-DQB1*0602 alleles.
Our results reveal an association of a cellular immune response to CHSP60, HLA class II alleles and IL-10 promoter genotypes in patients with chlamydial TFI.
Human Reproduction 09/2002; 17(8):2073-8. · 4.47 Impact Factor
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ABSTRACT: Chlamydia pneumoniae is an obligate intracellular pathogen with a tendency to cause persistent infections that has been associated with many chronic conditions such as asthma and coronary artery disease. However, its immunopathogenic mechanisms are poorly understood. When aiming to study the impact of C. pneumoniae infection on host cell apoptosis, we found that epithelial infected (HL) cells and macrophages (U937-line) were resistant to staurosporine and tumour necrosis factor (TNF)-alpha-induced physiological apoptosis 48, 72 or 120 h post-infection, as determined by flow cytometry, DNA fragmentation assay and fluorescence microscopy. The antiapoptotic influence was observed even at a late stage of the chlamydial life cycle and was dependent on the chlamydial protein synthesis. The mechanisms involved blockage of mitochondrial cytochrome c release and caspase 3 activation. We also found that during a persistent C. pneumoniae infection induced in vitro by penicillin treatment of cell cultures, the inhibition of apoptosis was extended for up to 120 h of follow-up post-infection and was restricted to the cells carrying chlamydial inclusions. Our findings suggest that inhibition of apoptosis may be one of the pathogenetic mechanisms by which C. pneumoniae infection can mediate the development of chronic diseases.
Scandinavian Journal of Immunology 05/2002; 55(4):390-8. · 2.23 Impact Factor
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ABSTRACT: The immunogenicity of pneumococcal polysaccharide (PS) vaccines can be improved by conjugating PS to a polypeptide carrier that alters the immune response from T-cell independent to T-cell dependent. In order to study the influence of PS or protein antigens as inducers of cell-mediated responses, 30 adults were immunized with a 23-valent pneumococcal PS vaccine (PS-group) or an 11-valent, tetanus and diphtheria mixed carrier conjugate vaccine with (adjuvant group) or without aluminium adjuvant (nonadjuvant group). Cell-mediated responses were analyzed on days 0, 14 and 28 after vaccination by measuring lymphocyte proliferation and production of interferon (IFN)-gamma (Th1 marker) or interleukin (IL)-4 and IL-5 (Th2 markers) cytokines after in vitro stimulation with the PS and protein components of the vaccines. Tetanus and diphtheria proteins were the main inducers of lymphocyte proliferative and cytokine responses. Conjugate vaccines induced increased proliferative responses to the tetanus or diphtheria protein, but not to the PS components. In the PS-group, a lymphocyte proliferative response to protein antigens was not observed. The number of antigen-specific and nonspecific IFN-gamma-secreting cells detected by ELISPOT tended to increase in all three groups in response to protein or to PS antigen. No major differences were detected in the number of IL-4-secreting cells measured 14 and 28 days after vaccination. The conjugate vaccine with adjuvant was associated with Th2 type of activation indicated by an enhanced IL-5 secretion in response to the tetanus and diphtheria protein antigens.
Scandinavian Journal of Immunology 05/2001; 53(4):422-8. · 2.23 Impact Factor
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ABSTRACT: Reliable markers for identifying infections in cancer patients on admission are lacking. The utility of the balance between interleukin (IL)-10 and IL-12 was analysed in this respect. The infection group (n=56) had higher median serum levels of IL-10 (3.8 pg/ml; interquartile range (IQR) 1.7-11.4 pg/ml versus 1.8 pg/ml; IQR 0.6-4.6 pg/ml; P=0.005) and IL-10 to IL-12 ratio (0.4; IQR 0.06-4.23pg/ml versus 0.05; IQR 0.02-0.31pg/ml; P<0.001) than the non-infection group (n=36). IL-10 and the ratio had the following figures of sensitivity (79%; 95% confidence interval (CI) 66-88 versus 39%; 95% CI 27-53), specificity (40%; 95% CI 12-74 versus 90%; 95% CI 56-100) and positive predictive value (88%; 95% CI 76-96 versus 96%; 95% CI 78-100) for identifying infections (56 cases with infection and 10 with neoplastic fever), and the corresponding area under curve (AUC) values for IL-10 and the ratio in identifying infections in general were 0.58; 95% CI 0.39-0.78 versus 0.64; 95% CI 0.46-0.82 and in bacteraemia 0.71; 95% CI 0.50-0.92 versus 0.75; 95% CI 0.58-0.93, respectively. Thus, IL-10 can be used as a screening method for identifying infections in cancer patients and the ratio of IL-10 to IL-12 for confirming the diagnosis.
European Journal of Cancer 05/2001; 37(7):857-61. · 5.54 Impact Factor
