Available via license: CC BY-NC 3.0
Content may be subject to copyright.
Yonsei Medical Journal
Vol. 47, No. 4, pp. 485 - 490, 2006
Yonsei Med J Vol. 47, No. 4, 2006
Infrared radiation is increasingly and uncritically used for
cosmetic and wellness purposes, despite the poorly understood
biologic effects of such treatments on humans. In the present
study, we investigated the effects of infrared radiation on col-
lagen and elastin production in dermal fibroblasts, as well as
the clinical and histopathologic effects of infrared radiation on
photo-aged facial skin lesions. In order to determine the effects
of infrared radiation on collagen and elastin production, dermal
fibroblasts were exposed to infrared radiation for varying
lengths of time and collagen and elastin contents were subse-
quently determined. Additionally, 20 patients with mild to
moderate facial wrinkles and hyperpigmented lesions received
daily treatments of far infrared radiation (900 to 1000 m) for
μ
six-months. During the treatment, patients and a medical
observer conducted independent photographic and clinical
evaluations every 4 weeks, and skin biopsies were obtained for
histological analysis at baseline and one month post-treatment.
We found that the content of collagen and elastin produced
by the fibroblasts increased after infrared radiation, and that
this increase was proportional to the duration of irradiation ex-
posure. Following 6 months of treatment, all patients reported
good (51-75%) improvements in skin texture and roughness.
Additionally, patients noted fair (25-50%) improvement in
color tone of the skin; however, improvements in hyperpig-
mented lesions were not observed. Objective medical evalua-
tion of the patients indicated that roughness and laxity were
fairly improved, but there was no significant improvement in
hyperpigmented lesions. Histological examination failed to
reveal any differences as well. These results suggest that in-
frared radiation may have beneficial effects on skin texture and
wrinkles by increasing collagen and elastin contents from the
stimulated fibroblasts. Therefore, skin treatment with infrared
radiation may be an effective and safe non-ablative remodeling
method, and may also be useful in the treatment of photo-aged
skin.
Key Words: Infrared radiation, fibroblasts, photo-aging
INTRODUCTION
As the outermost barrier, human skin is in
direct contact with numerous environmental
factors including solar radiation, which is one
cause of photo-aging. Characterized clinically by
wrinkles, mottled pigmentation, rough skin, and
loss of skin tone, the major histologic alterations
associated with photo-aging lie in dermal con-
nective tissue. A variety of highly effective, abla-
tive methods have been used to treat the facial
skin lesions associated with photo-aging; how-
ever, most patients complain of discomfort during
the treatment and must also be concerned with
the risk of infection and scarring, as ablative
methods completely disrupt or remove the epi-
dermis in a direct manner. The primary mecha-
nism for treatment of photo-aged skin lesions by
these methods appears to be through the deposi-
tion of new extracellular matrix elements.
1-3
Nonablative dermal remodeling (NDR), a recently
developed procedure also called non-ablative skin
rejuvenation or subsurfacing, does not disrupt the
epidermis, and is a better tolerated alternative to
ablative laser resurfacing. NDR is designed to
selectively confine thermal injuries of the papil-
lary and upper reticular dermis without causing
epidermal damage, and thus induce fibroblast
activation and synthesis of new collagen and ex-
tracellular matrix material.
4
In contrast to detailed
studies of ultraviolet radiation responses, little is
known about the biologic effects of infrared (IR)
radiation. IR radiation exists in the invisible por-
Effects of Infrared Radiation on Skin Photo-Aging and
Pigmentation
Ju Hee Lee, Mi Ryung Roh, and Kwang Hoon Lee
Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Received November 8, 2005
Accepted January 26, 2006
Reprint address: requests to Dr. Kwang Hoon Lee, Department
of Dermatology, Yonsei University College of Medicine, 134
Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-
2228-2080, Fax: 82-2-393-9157, E-mail: kwanglee@yumc.yonsei.
ac.kr
Ju Hee Lee, et al.
Yonsei Med J Vol. 47, No. 4, 2006
tion of the electromagnetic spectrum, and is ad-
jacent to the long wavelength of the visible light
range that extends up to the microwave range.
Several studies have shown that IR radiation pro-
duces a temperature-independent stimulatory
effect on the proliferation of human fibroblasts
and collagen synthesis in vivo.
5,6
However, since
IR radiation is increasingly and uncritically used
for cosmetic and wellness purposes, the present
study was undertaken to investigate the effects of
IR radiation on collagen and elastin production in
dermal fibroblasts and determine its clinical and
histologic effects on photo-aged facial skin lesions
including facial wrinkles, roughness, tightness,
and hyperpigmented lesions.
MATERIALS AND METHODS
Culture of human dermal fibroblasts
Primary human dermal fibroblast cultures, es-
tablished by explanting tissue specimens obtained
from neonatal foreskin, were utilized in pas-
sages.
3-8
All cell cultures were maintained in
Dulbecco's Modified Eagle's Medium (DMEM)
supplemented with 10% fetal calf serum and 2
mM glutamine.
IR treatment
Human dermal fibroblasts were exposed in vitro
to infrared (IR) radiation, and an IR radiation
emitting device (MG Care , Seoul, Korea) was
used as the source. This device emits far IR radia-
tion (900 to 1000 m) with an energy flux of 35
μ
mW/cm
2
. Human dermal fibroblasts were ex-
posed to IR radiation for 1 to 5 hours. Collagen
and elastin assays were performed after a 24-hour
post-irradiation incubation period. Results were
compared with a control group which was not
exposed to IR radiation.
Collagen and elastin assay
Collagen assays were performed using the
Sircol collagen assay kit (Biocolor, UK) according
to manufacturer's instructions. Briefly, the collect-
ed supernatant was centrifuged at 1,500 rpm for
4 min to isolate the extracellular matrix, and 100
l of the resulting supernatant was mixed with 1
μ
ml of Sircol dye for 30 min and centrifuged at
10,000 rpm for 5 min to isolate the formed colla-
gen-dye complex. After decanting the suspen-
sion, droplets were dissolved in 1 ml Sircol alkali
reagent and assessed at 513 nm by spectropho-
tometry. Total soluble collagen was expressed as
a concentration ( g/mL) relative to control fibro
μ
-
blasts that did not receive infrared radiation.
Similarly, soluble elastin content was deter-
mined according to Fastin Elastin Assay instruc-
tions
7
and with the use of a commercial kit con-
taining the dye label 5,10,15,20-tetraphenyl-21-23
porphrine sulphonate (Biocolor Ltd, Belfast, Eng-
land).
Both assays were performed 3 times and results
were obtained by averaging the data.
Patients and methods
Twenty females (ages 35-61; mean 44.3 years,
skin phototypes III-IV) with facial wrinkles and
hyperpigmented lesions were enrolled in the
study from March to October, 2004. Patients re-
ceived 15-20 minute daily treatments (on 5 week-
days) of far IR radiation for a period of 6 months.
The emitting device, which was made of medical
silicon, covered the entire face except for the eyes,
mouth, and nostrils; the temperature of the device
was approximately 32.0 to 35.0 and the radia-
tion energy was 35 mW/cm
2
. Photographic docu-
mentation was taken after 0, 3, and 6 months of
treatment, and clinical improvement scores were
determined every 4 weeks. All of the patients
completed the six-month treatment session and
were able to return for follow-up evaluations.
Each patient and a medical observer indepen-
dently performed clinical assessments using a
well-established grading scale of 0 = < 25% (mini-
mal), 1 = 26-50% (fair), 2 = 51-75% (good), 3 = 75-
90% (excellent), 4 = 91-100% (clear) improvement.
Assessment categories included improvements in
small wrinkles, color tone, brown spots, rough-
ness and tightness. Average improvement scores
were calculated as the mean of the grading scales
of all categories. Categories of the clinical assess-
ment by the medical observer included fine wrin-
kles, coarse wrinkles, roughness, mottled
Effects of Infrared Radiation on Skin Photo-Aging and Pigmentation
Yonsei Med J Vol. 47, No. 4, 2006
hyperpigmentation, laxity, and skin tone. Standar-
dized photographs and dermoscopic observations
(Coscam CCL-205, Sometech Cosmetic, Seoul,
Korea) were reviewed to help the medical ob-
servers identify each clinical grade. Skin biopsies
with a 2-mm punch were performed on the cheeks
for hyperpigmented lesions and on the lateral
sides of eyes for wrinkles prior to treatment and
1 month after final treatment. In addition to hema-
toxylin-eosin stain, special stains such as elastic
stain and Masson-trichrome stain were performed
to verify the difference in amount of elastic and
collagen fibers in the dermis. Side effects were
recorded and rated in severity (0 = none, 1 = mild,
2 = moderate, 3 = severe) at each follow-up visit.
We performed a Wilcoxon rank sum test (SAS
version 8.2) to compare the treatment effects
between the two groups and a Shapiro-Wilk test
(SAS version 8.2) to compare baseline and post-
treatment measurements.
RESULTS
Collagen and elastin assay
Total soluble collagen was increased 2 hours
after IR radiation exposure, relative to controls,
and total content increased with the duration of
IR radiation exposure (Fig. 1); the results were an
average of three measurements. The concentration
of total soluble collagen in the control was 4.6 g/
μ
mL, and in treatment groups the concentrations
increased to 3.18 g/mL, 13.37
μ
g/mL, 19.77
μ
g/
μ
mL, 29.23 g/mL, and 36.46
μ
g/mL with 1, 2, 3, 4,
μ
and 5 hours of IR treatment, respectively. Soluble
elastin also increased 1 hour after infrared radia-
tion compared to the control. Similar to collagen,
the content of soluble elastin increased with
longer durations of irradiation (Fig. 2). The con-
centration of soluble elastin in the control was 4.58
g/mL, and in treatment groups the concen
μ
-
trations of soluble elastin increased to 9.17 g/mL,
μ
15.1 g/mL, 17.61
μ
g/mL, 26.84
μ
g/mL, and 29.31
μ
g/mL, with 1, 2, 3, 4, and 5 hours of irradiation
μ
treatment, respectively.
Fig. 3. Clinical improvement scores (Patient evaluation).
The average improvement score as determined by the
patient was 1.88. Roughness and tightness were the most
improved categories with a grading scale of 2.55 and 2.45,
respectively. Hyperpigmented lesions, however, showed
minimal improvement.
Fig. 1. Concentrations of total soluble collagen after IR
irradiation. Total soluble collagen increased after 2 hours
of infrared radiation compared to control. Concentrations
increased with irradiation duration.
Fig. 2. Concentration of soluble elastin after IR irradiation.
Soluble elastin increased after 1 hour of infrared radiation
compared to control. Concentration of soluble elastin in-
creased with irradiation duration.
Ju Hee Lee, et al.
Yonsei Med J Vol. 47, No. 4, 2006
Clinical evaluation
The average improvement score, as evaluated
by patients, was 1.88, which was statistically sig-
nificant (p < 0.05). The grading scale in the
category of roughness and tightness was 2.55 and
2.45, respectively, indicating a 51-75% impro-
vement. The grading scale of skin color tone was
1.95. The grading scale of small wrinkles was 1.8,
indicating fair improvement (26-50%). Unlike the
previous categories, however, hyperpigmented
lesions showed minimal improvement (Fig. 3).
The average grading scale, as evaluated by a
medical observer, was 1.31, which was also statis-
tically significant (p < 0.05). Roughness was the
most improved category, with a grading scale of
2.45 (Fig. 4). Fine wrinkles were at least fairly
improved (26-50%) in all patients with the grading
scale of 1.9; however, coarse wrinkle showed
minimal improvement (Fig. 5). Skin tone and
laxity, with a grading scale of 1.1 and 1.2, respec-
tively, were fairly improved (26-50%) in all 20
patients, and hyperpigmented lesions did not
show any statistically significant improvement.
Histolopathologic evaluation
Histopathologic examinations indicated that
there was no significant difference in the basal
hyperpigmentation after 6 months of treatment
relative to the control group. Neither the depth
nor the amount of solar elastosis in the dermis
was significantly different after 6-months of
treatment with IR radiation. There were no dif-
ferences noted between the two groups using
special stains such as elastin stain or Masson-
trichrome stain.
Fig. 4. Clinical improvement scores (Medical observer
evaluation). The average improvement score as deter-
mined by a medical observer was 1.2. Roughness was the
most improved category with a grading scale of 2.45. Fine
wrinkles were at least fairly improved in all patients, with
the grading scale of 1.9. There was minimal improvement
in the coarse wrinkle category.
Fig. 5. Photographic evaluation of facial
wrinkles. Improvement of facial wrinkles after
6 months (A: Baseline, B: after 6 months).
Effects of Infrared Radiation on Skin Photo-Aging and Pigmentation
Yonsei Med J Vol. 47, No. 4, 2006
Side effects
In general, any side effects of infrared radiation
treatment were minimal and transient. Of the 20
patients treated, 80% developed mild transient
erythema, which lasted only a few hours after the
treatment and was not a significant problem for
the patients. Other complaints included mild dry-
ness (3 patients) and scaling of the face (2
patients). One patient experienced exacerbation of
perioral dermatitis, which subsided without any
treatment. There were no instances of pigmentary
alteration or burns due to treatment, and all of the
treatment sessions were generally well tolerated
with minimal complaints.
DISCUSSION
Infrared (IR) radiation is an invisible portion of
the electromagnetic spectrum adjacent to the long
wavelength of the visible light range and extends
to the microwave range. IR radiation consists of
wavelength ranging from 0.75 to 1000 m (0.75
μ
m
μ
= 750 nm),
8
and can be subdivided into near (0.75
to 3 m), middle (3 to 30
μ
m), and far (30 to 1000
μ
m). The device used in this study emits far IR
μ
radiation that elevates the skin temperature to a
pleasant 32 to 35 . Recently, nonablative collagen
remodeling techniques have emerged as a means
to avoid side effects such as oozing and erythema
due to the complete removal of the epidermis in
direct ablative methods. There is some evidence
that the underlying mechanism of this action is
the induction of new collagen growth due to ther-
mal damage of the dermis.
9,10
Using this concept,
the need for gross damage of the epidermis
merely to improve the surface may be unneces-
sary, as thermal effects to the dermis, without sub-
sequent injury to the epidermis, can be induced
with IR radiation.
9
Therefore, we investigated the
effects of IR radiation on collagen and elastin pro-
duction in fibroblasts as well as the clinical and
histopathologic effects of infrared radiation on
facial skin, especially on photo-aged skin lesions
such as roughness, tightness, wrinkles, and hyper-
pigmentation.
Our study showed that IR radiation increased
the amount of total soluble collagen and soluble
elastin in fibroblasts and demonstrated that could
result in clinical improvement in skin texture. The
clinical effects were, however, gradual, with a
mean improvement of 25% to 50% achieved after
6 months of treatment, and roughness and tight-
ness of the skin was improved in all of the 20
patients enrolled in the study. Fine wrinkles were
at least fairly improved in all patients, but hyper-
pigmented lesions of the skin were not affected
with IR radiation. This finding was further sup-
ported by histopathologic examination, which did
not reveal any discernable differences in basal
hyperpigmentation. IR irradiation has been re-
ported to cause skin changes similar to those
found in solar UV irradiation-induced elastosis;
10,11
however, in the present study, there was no
difference in the depth or amount of solar
elastosis after 6 months of treatment with IR
radiation.
Many reports have indicated that that IR radia-
tion may have a stimulatory effect on the pro-
liferation of human fibroblasts and collagen
synthesis during wound healing.
3,5,9
Toyokawa
9
et
al. reported that greater collagen regeneration and
infiltration of fibroblasts expressing transforming
growth factor- 1 (TGF- 1) is observed in rat skin
β β
after irradiation with far infrared radiation. The
cytokine TGF- 1 is well known to accelerate
β
wound healing
12
by stimulating fibroblasts to
produce extracellular matrix proteins, including
collagen and fibronectin, and to also facilitate
their deposition.
13,14
Several in vivo studies have
also demonstrated that near-IR rays and IR radia-
tion emitting lasers can have therapeutic effects on
wound healing by promoting collagen synthesis,
cell proliferation, and keratinocyte motility.
15,16
The production of collagen fibers from activated
fibroblasts by IR radiation has been suggested as
a possible mechanism for the therapeutic effect on
wound healing; however, there are no reports as
of yet, other than for wound healing, that explain
the mechanisms of treatment effects of IR radia-
tion on aging or wrinkling. While our culture
results may or may not extrapolate to clinical
results, our study showed that infrared radiation
may have proliferative effects of fibroblasts in
either an in vivo or in vitro environment. The re-
sults of this study, however, are limited, as the in
vivo clinical results do not prove any changes in
Ju Hee Lee, et al.
Yonsei Med J Vol. 47, No. 4, 2006
fibroblastic activity. We evaluated fibroblastic
activity in vivo by comparing the histopathology
using collagen and elastin stains; however, this
method may have been insufficient for comparing
minute differences of collagen and elastin produc-
tion in fibroblasts. The results suggest that the
improvement of texture of the skin may have
resulted from increased collagen and elastin in the
dermis. Further, thermal effects of infrared radia-
tion may have a role in activating fibroblasts, but
additional studies regarding the abundance of
cytokines in proliferating fibroblasts are needed.
The side effects of treatment with the IR radia-
tion were minimal in this study. The severity and
duration of erythema observed post-treatment
was mild and resolved by 30 minutes post- treat-
ment. In addition, there was no histopathologic
evidence of remarkable inflammation, IR radiation
burns, or increased solar elastosis. This suggested
that IR radiation treatment at an ambient tempera-
ture is safe and does not cause harmful thermal
injuries. Our results further suggest that IR radia-
tion may result in beneficial effects on skin texture
and wrinkles by increasing collagen and elastin in
the dermis through stimulation of fibroblasts.
Thus, treatment with IR radiation may be an effec-
tive and safe non-ablative remodeling method of
the skin, and it may have some use as a suppor-
tive method in the treatment of photo-aged skin.
Elucidation of the exact photophysical and photo-
chemical mechanisms triggered by IR radiation as
well as future studies of the practicality of IR
radiation treatment may reveal novel therapeutic
applications of IR radiation in clinical derma-
tology.
REFERENCES
1. Stuzin JM, Baker TJ, Baker TM, Kligman AM. His-
tologic effects of the high-energy pulsed CO
2
laser on
photoaged facial skin. Plast Reconstr Surg 1997;99:
2036-55.
2. Ross EV, McKinlay JR, Sajben FP, Miller CH, Barnette
DJ, Meehan KJ, et al. Use of a novel erbium laser in
a Yucatan minipig: a study of residual thermal damage,
ablation, and wound healing as a function of pulse
duration. Lasers Surg Med 2002;30:93-100.
3. Seckel BR, Younai S, Wang KK. Skin tightening effects
of the ultrapulse CO
2
laser. Plast Reconstr Surg 1998;
102:872-7.
4. Nelson JS, Majaron B, Kelly KM. What is nonablative
photorejuvenation of human skin? Semin Cutan Med
Surg 2002;21:238-50.
5. Mester E, Mester AF, Mester A. The biomedical effects
of laser application. Lasers Surg Med 1985;5:31-9.
6. Castro D, Abergel R, Meeker C, Dwyer R, Lesavoy M,
Uitto J. Effects of the Nd:YAG laser on DNA synthesis
and collagen production in human skin fibroblasts
cultures. Ann Plast Surg 1983;11:214-22.
7. Pawlicka E, Bankowski E, Jaworski S. Elastin of the
umbilical cord arteries and its alterations in EPH
gestosis (preeclampsia). Biol Neonate 1999;75:91-6.
8. Phillips M. Electromagnetic radiation. In: The new
encyclopedia britannica. vol 6. 15th ed. Chicago: Ency-
clopedia Britannica Inc; 1985. p.644-65.
9. Khan MH, Sink RK, Manstein D, Eimeri D, Anderson
RR. Intradermally focused infrared laser pulses: ther-
mal effects at defined tissue depths. Lasers Surg Med
2005;36:270-80.
10. Toyokawa H, Matsui Y, Uhara J, Tsuchiya H, Teshima
S, Nakanishi H, et al. Promotive effects of far-infrared
ray on full-thickness skin wound healing in rats. Exp
Biol Med 2003;228:724-9.
11. Kligman LH. Intensification of ultraviolet-induced
dermal damage by infrared radiation. Arch Dermatol
Res 1982;272:229-38.
12. Yu W, Naim JO, Lanzafame RJ. Expression of growth
factors in early wound healing in rat skin. Lasers Surg
Med 1994;15:281-9.
13. Postlethwaite AE, Keski-Oja J, Moses HL, Kang AH.
Stimulation of the chemotactic migration of human
fibroblasts by transforming growth factor . J Exp Med
β
1987;165:251-6.
14. Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL,
Kang AH. Transforming growth factor- increases
β
steady-state levels of type 1 procollagen and fibronectin
messenger RNAs posttranscriptionally in cultured
human dermal fibroblasts. J Clin Invest 1987;79:1285-8.
15. Singer AJ, Clark RA. Cutaneous wound healing. N
Engl J Med 1999;341:738-46.
16. O'kane S. Ferguson MW. Transforming growth factor
s and wound healing. Int J Biochem Cell Biol 1997;29:
β
63-78.