ARTICLE IN PRESS
Journal of Photochemistry and Photobiology B: Biology 77 (2004) 93–96
www.elsevier.com/locate/jphotobiol
Short communication
Inhibition of immediate type hypersensitivity reaction by
combined irradiation with ultraviolet and visible light
Andrea Koreck a, Zsanett Csoma a, Marta Boros-Gyevi a, Ferenc Ignacz b,
Laszlo Bodai a, Attila Dobozy c, Lajos Kemeny a,c,*
a
Department of Dermatology and Allergology, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary
b
Department of Optics and Quantum Electronics, University of Szeged, H-6701 Szeged, Hungary
c
Dermatological Research Group of the Hungarian Academy of Sciences Szeged, H-6701, Szeged, Hungary
Received 19 May 2004; received in revised form 9 August 2004; accepted 13 August 2004
Abstract
Recently we found that ultraviolet B (UVB) irradiation in erythematous doses significantly inhibited the immediate type hypersensibility reaction in the skin. In the present study we investigated the effects of different wavelengths on the skin prick test reaction
(SPT). The forearm of ragweed allergic patients was irradiated with increasing doses of ultraviolet A (UVA), visible light (VIS) or
combined UVB, UVA and VIS light, referred to as mUV/VIS. SPTs were performed 24 h after irradiation both on irradiated and
non-irradiated control skin areas using ragweed extract. UVA and VIS irradiation led to a slight, not significant inhibition of allergen-induced wheal formation. Mixed irradiation with mUV/VIS light resulted in a dose-dependent inhibition of the allergen-induced
wheal formation. The inhibition was significant already at suberythematous doses. As there is a good correlation between SPT and
the nasal symptoms in patients with hay fever these data suggest that phototherapy with mUV/VIS light might be an effective and
safe treatment modality for immediate type hypersensibility reactions in the skin and nasal mucosa.
Ó 2004 Elsevier B.V. All rights reserved.
Keywords: Immediate type hypersensitivity; Skin prick test; Phototherapy
1. Introduction
Phototherapy has a profound immunosuppressive effect and phototherapeutic methods utilizing both ultraviolet (UV) and visible (VIS) light are therefore widely
used for the therapy of various inflammatory skin diseases such as psoriasis and atopic dermatitis [1–4]. It
has been also shown that UV irradiation of skin inhibits
the development of contact hypersensibility and induces
hapten-specific tolerance, which can be adoptively transferred in mice. The major mechanisms of immunosuppression induced by the various forms of phototherapy
in the skin involve apoptosis induction in infiltrating T
*
Corresponding author. Tel.: +36 30 5152 884; fax: +36 62 545 954.
E-mail address: [email protected] (L. Kemeny).
1011-1344/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jphotobiol.2004.08.008
cells, reduction in the number and function of Langerhans cells, and the induction of immunomodulatory
cytokines such as IL-10 [5–8].
Recently, we have found that UVB irradiation was
capable to significantly inhibit the immediate type
hypersensibility reaction in the skin at erythematous
doses and that 308 nm xenon chloride (XeCl) eximer laser is effective for the treatment of allergic rhinitis [9].
The goal of our present study was to evaluate the effect
of different wavelengths on the immediate type hypersensibility in the skin. As skin prick test (SPT) is the
most widely used in vivo test for the diagnosis of immediate type allergic reaction we tested the capacity of different wavelengths to inhibit the wheal formation in
SPT on irradiated and non-irradiated skin areas. We
found that mixed irradiation with UVB, UVA and
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A. Koreck et al. / Journal of Photochemistry and Photobiology B: Biology 77 (2004) 93–96
2. Materials and methods
repeated measures ANOVA, followed by DunnettÕs
multiple-comparison test. SpearmanÔs rank correlation
test was applied to analyze the correlation between the
irradiation doses and the inhibition of wheal formation.
Differences were considered significant at p < 0.05.
2.1. Effect of different wavelengths on the immediate
hypersensitivity reaction in the skin
3. Results
visible light is capable to inhibit SPT reaction even after
a single irradiation with suberythematous doses.
2.1.1. Patients
The study protocol was approved by the Human
Investigation Review Board of the Szeged University.
Informed consent was obtained from 19 patients with
a history of at least 2 years of ragweed-induced allergic
rhinitis, 7 men and 12 women, aged 21–58 years (mean
age 32.98 years) with skin types II/III. Patients discontinued tacking any treatment 2 weeks prior to the performance of SPTs. All patients had a positive SPT
with a wheal formation of at least 10.0 mm in diameter.
2.1.2. Irradiation protocol
Five patients received UVA irradiation (WaldmannPUVA 4000, Germany, range: 320–400 nm). On one
forearm three areas were irradiated with increasing
doses of UVA (0.5, 1 and 2 J/cm2). Seven patients were
irradiated with increasing doses of visible (VIS) light (2,
4, 6 and 8 J/cm2) (Rhinolight-VIS, Hungary, range: 395–
600 nm). In 7 patients irradiation was performed with
increasing doses of mixed UVB (5%), UVA (25%) and
VIS (70%), referred to as mUV/VIS light (2, 4, 6 and 8
J/cm2) (Rhinolight-mUV/VIS, Hungary, range: 310–
600 nm). Measurements were performed with Scientech
Vector H410 (Scientech Inc., Boulder, CO) and JobinYvon H-20UV (Ocean Optics, RK Duiven, The
Netherlands).
2.1.3. Skin prick test
The SPT is a method that is widely used to investigate
the immediate hypersensitivity reaction to a specific
allergen in the skin [10,11]. SPTs were performed with
ragweed extract (Soluprick-Epipharm Allergie-Service
GmbH) on the irradiated skin areas from one forearm
and non-irradiated control skin areas from the other
forearm, 24 h after irradiation. Twenty-microlitre aliquots of the test solution were placed on the patientsÕ forearm, with a distance of more than 3 cm between
individual application sites. Sterile 0.9% sodium chloride
solution and histamine hydrochloride were used for negative and positive controls respectively. The test results
were evaluated after 20 min and the induced wheal
was measured by digital planimetry.
2.2. Statistical analyses
The differences in wheal formation after irradiation
were analyzed statistically by means of Friedman
UVA irradiation resulted in a slight inhibitory effect
on allergen-induced wheal formation (Fig. 1(a)). The
inhibition rate was 8.97% at 0.5 J/cm2, 14.22% at 1 J/
cm2 and 10.13% at 2 J/cm2, but the changes did not
reach statistical significance (p = 0.069). No correlation
was found between the inhibition of allergen-induced
wheal formation and the UVA dose.
Similar results, mirrored by a slight, statistically not
significant inhibition of wheal formation, were obtained
24 h after VIS irradiation (Fig. 1(b)). The inhibition was
6.5% at 2 J/cm2, 7.19% at 4 J/cm2, 6.11% at 6 J/cm2 and
6.74% at 8 J/cm2, at neither of these doses changes proof
to be significant (p = 0.406). No correlation was found
between the inhibition of allergen-induced wheal formation and the VIS dose.
Mixed irradiation with mUV/VIS light resulted in a
dose-dependent inhibition of the allergen-induced wheal
formation (r = 0.463, p = 0.0132) (Fig. 1(c)). The inhibition was 33.92% at 2 J/cm2, 54.74% at 4 J/cm2, 68.96% at
6 J/cm2 and 82.87% at 8 J/cm2. The inhibition was statistically significant at the doses of 4, 6 and 8 J/cm2
(p < 0.05). The two lowest doses did not produce erythema on the skin, the proportion of UVB light in
mUV/VIS was 0.1 J/cm2 for 2 J/cm2 and 0.2 J/cm2 for
4 J/cm2. The use of higher, erythematosus doses of
mUV/VIS light (0.4 J/cm2 UVB for 8 J/cm2 mUV/VIS)
led to almost complete inhibition of wheal formation.
4. Discussion
The goal of our study was to assess the inhibitory effect of different wavelengths on the immediate-type
hypersensibility reaction. We evaluated the inhibitory
effect on the antigen-induced wheal formation in SPT.
Although, we found that UVA and VIS light alone
had only a slight inhibitory effect on immediate type
skin test reaction, the addition of these wavelengths to
UVB light in the form of mUV/VIS, resulted in a synergistic effect. We have previously found that UVB irradiation with the 308 nm XeCl excimer laser significantly
suppressed allergen-induced wheal development only
at erythematous doses [9]. In the present study we found
that a single irradiation with a suberythematous dose of
UVB resulted in an inhibition of SPT when irradiation
was performed using a combination of UVB, UVA
and VIS light (mUV/VIS). Vocks et al. found compara-
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(a)
UVA
Inhibition (%)
100
n=5
80
80
60
60
40
40
20
20
0
0.5
(c)
1
J/cm2
2
n=7
0
2
4
6
8
J/cm2
mUV/VIS
100
Inhibition (%)
VIS
(b) 100
80
n=7
*
*
*
60
40
20
0
2
4
6
8 J/cm
2
Fig. 1. The inhibitory effects of different wavelengths on wheal formation in SPT. Irradiation with increasing doses of UVA light resulted in a slight,
not significant inhibition of wheal formation in SPT (a). Irradiation with increasing doses of VIS light resulted in a slight, not significant inhibition of
wheal formation (b). Irradiation with increasing doses of mUV/VIS light resulted in a significant, dose dependent inhibition of wheal formation in
SPT (c). Significant decreases (*p < 0.05) were observed 24 h after irradiation at 4 J/cm2 (p = 0.01), at 6 J/cm2 (p < 0.001) and at 8 J/cm2 (p < 0.001).
ble inhibition rates of wheal formation (48%) only after
three irradiation with suberythematous doses of UVB
[12]. These results suggest that mUV/VIS irradiation
has a more profound and rapid inhibitory effect on
immediate type skin reaction than UVB alone. The
underlying mechanism might be the synergistic effect
of different wavelengths on histamine release. In the skin
prick test, the antigen induces a rapid release of histamine from the sensitized cells and results in the development of a wheal in 10–20 min. It has been shown that
UVA light significantly inhibited histamine release from
human basophils and a human mast cell line and that
UVB light had an inhibitory effect only on mast cells
[13]. The effect of in vitro UVA irradiation of basophils
is characterized by a biphase dose dependent action on
histamine release: low doses are followed by a significant
inhibitory effect, in contrast high doses are followed by
histamine eliberation [14]. The strong inhibition of
SPT reaction by mUV/VIS might therefore be explained
by the combined actions of the different wavelengths on
the skin mast cells.
We reported recently that UVB irradiation of the nasal mucosa with medium doses of XeCl laser resulted in
the significant improvement of clinical symptoms of hay
fever, while low doses had no effect [9]. An important
step towards the application of phototherapy for the
treatment of allergic rhinitis is to identify the clinically
effective wavelengths, which combine the advantages
of high efficacy and few side effects. It is well known that
repeated irradiation with UV light in high doses has a
carcinogenic potential and this depends on the cumulative dose [15]. Although, the UVB doses we used for the
treatment of allergic rhinitis were much lower than those
leading to an increased risk of cancer; reduction of UVB
doses might further improve safety of intranasal
phototherapy.
Our data showed that comparable inhibitory effect
on allergen-induced wheal formation might be
achieved by irradiation with suberythematous doses
of mUV/VIS light as with higher erythematous doses
of UVB alone. It has been shown that there is a good
correlation between the SPT reaction and the nasal
symptoms in patients with hay fever and that reduced
immediate skin sensitivity is observed after long-term
successful immunotherapy [10,11]. These data suggest
that phototherapy with mUV/VIS light might be effective not only in inhibiting immediate type hypersensitivity in the skin but also in the nasal mucosa and
that phototherapy using mUV/VIS light might be an
effective and safe treatment modality for allergic
rhinitis.
5. Abbreviations
MED
mUV/VIS
SPT
minimum erythema dose
mixed ultraviolet and visible light
skin prick test
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UV
UVB
UVA
XeCl
VIS
A. Koreck et al. / Journal of Photochemistry and Photobiology B: Biology 77 (2004) 93–96
ultraviolet
ultraviolet B
ultraviolet A
xenon chloride
visible
Acknowledgement
This study was supported by the NKFP 1A/0012,
OMFB 01620 and ETT 419/2003 grants.
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