Real-life experience in the treatment of solar urticaria: retrospective cohort study.

BACKGROUND: Solar urticaria (SU) is a rare photodermatosis causing a significant impact on patients' quality of life (QoL), and treatment is often challenging. AIM: To analyse clinical experience with a tailored stepwise therapeutic approach. METHODS: A retrospective cohort design was used. Patients with suspected SU underwent laboratory investigations and photoprovocation. Those with a high minimal urticaria dose (MUD) were treated with a single antihistamine (protocol 1), and those with a lower MUD received three types of antihistamines (protocol 2); both protocols included a leucotriene receptor antagonist (LRA). In cases of failure, treatment was switched to omalizumab at doses of < 300 mg/month with incremental dosage increases as necessary (monthly dose range, 150-600 mg/month). Symptom relief and photoprovocation under treatment were evaluated. RESULTS: In total, 30 patients (10 men, 20 women) were enrolled. Most (87%) were sensitive to visible light (1-70 J/cm2 ) with or without extension to ultraviolet A. Of the 30 patients, 23 opted for our stepwise approach: 22 achieved complete remission on protocols 1 or 2 (n = 17) or after switching to omalizumab (n = 5), and another patient achieved partial remission under omalizumab. There were no treatment-related severe adverse effects. CONCLUSIONS: Symptoms of SU can be well controlled by treatment with antihistamines and an LRA tailored to the degree of photosensitivity, followed by omalizumab in refractory cases. This has important implications for patient QoL.

Integrated cooling-vacuum-assisted 1540-nm erbium:glass laser is effective in treating mild-to-moderate acne vulgaris.

Acne treatment by a mid-infrared laser may be unsatisfactory due to deeply situated acne-affected sebaceous glands which serve as its target. Skin manipulation by vacuum and contact cooling may improve laser-skin interaction, reduce pain sensation, and increase overall safety and efficacy. To evaluate the safety and efficacy of acne treatment using an integrated cooling-vacuum-assisted 1540-nm erbium:glass laser, a prospective interventional study was conducted. It included 12 patients (seven men and five women) suffering from mild-to-moderate acne vulgaris. The device utilizes a mid-infrared 1540-nm laser (Alma Lasers Ltd. Caesarea, Israel), which is integrated with combined cooling-vacuum-assisted technology. An acne lesion is initially manipulated upon contact by a vacuum-cooling-assisted tip, followed by three to four stacked laser pulses (500-600 mJ, 4 mm spot size, and frequency of 2 Hz). Patients underwent four to six treatment sessions with a 2-week interval and were followed-up 1 and 3 months after the last treatment. Clinical photographs were taken by high-resolution digital camera before and after treatment. Clinical evaluation was performed by two independent dermatologists, and results were graded on a scale of 0 (exacerbation) to 4 (76-100 % improvement). Patients' and physicians' satisfaction was also recorded. Pain perception and adverse effects were evaluated as well. All patients demonstrated a moderate to significant improvement (average score of 3.6 and 2.0 within 1 and 3 months, respectively, following last treatment session). No side effects, besides a transient erythema, were observed. Cooling-vacuum-assisted 1540-nm laser is safe and effective for the treatment of acne vulgaris.

Noninvasive in vivo confocal laser scanning microscopy is effective in differentiating allergic from nonallergic equivocal patch test reactions.

Patch testing is the gold standard for the validation of contact dermatitis. It relies on the subjective scoring by an evaluator of the inflammatory reaction induced by an allergen applied to the skin. Equivocal reactions imply faint erythema and could represent allergic, irritant, or negative reactions. They constitute approximately 1 % of the positive reactions encountered in patch test practice. Histological evaluation of the equivocal reaction has proven helpful for the correct interpretation but is however time consuming, and its invasive nature is often unacceptable to the patient. In vivo confocal laser scanning microscopy (CLSM) is a novel, noninvasive imaging technique which permits real-time visualization of skin structures and lesions at a resolution close to that obtained by conventional histology. CLSM has been successfully applied for the differentiation between clinically clear-cut allergic and irritant patch test reactions. The objective of this study is to determine the relevance of CLSM in differentiating between allergic, irritant, and negative equivocal patch test reactions. Fifteen patients who underwent patch testing in our clinic were observed as having 20 equivocal reactions. All 20 reactions were evaluated using in vivo CLSM and compared with adjacent normal skin. In vivo CLSM evaluation revealed that 8 of the 20 equivocal reactions (40 %) showed confocal patterns consistent with the patterns encountered in positive allergic reactions. Anamnestic exposure, i.e., detailed assessment of previous related contact with these allergens, confirmed high relevance rates. In vivo CLSM is useful in differentiating between allergic, irritant, and negative equivocal patch test reactions, a differentiation that cannot be made by conventional clinical patch test reading.

Cutaneous leishmaniasis responds to daylight-activated photodynamic therapy: proof of concept for a novel self-administered therapeutic modality.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Israel, with hundreds of new cases reported in recent years. Photodynamic therapy (PDT) is highly effective for treatment of CL, but requires equipment available only at specialized centres. Daylight-activated PDT (DA-PDT) abolishes the need for artificial light sources and allows the patient to administer the treatment with no professional assistance. OBJECTIVES: The objective of this single-centre, open study was to establish proof of concept for the efficacy of DA-PDT in the treatment of CL using clinical, microbiological and molecular clearance as outcome measures. METHODS: Thirty-one patients with CL (11 Leishmania major and 20 Leishmania tropica) underwent DA-PDT. Fourteen patients were treated in the hospital garden under professional supervision and 17 patients underwent DA-PDT as a self-administered treatment modality at home. Following application of a thick layer of 16% methyl aminolaevulinate and 30-min occlusion, the lesions were exposed to daylight for 2·5 h. Treatment sessions were repeated at weekly intervals until clinical and microbiological cure. Control lesions were either treated with cryotherapy or left untreated. RESULTS: The overall cure rate for DA-PDT was 89% (intention-to-treat cure rate 77%); this was 86% for the hospital-based treatment group and 92% for the self-administered group. CONCLUSIONS: DA-PDT proved to be effective in the treatment of CL caused by L. major and L. tropica. More patients were treated according to a self-administered protocol, suggesting that DA-PDT can be adopted even in technologically deprived countries where the majority of Leishmania infections are encountered.

Late-onset onchocercal skin disease among Ethiopian immigrants.

BACKGROUND: Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. OBJECTIVES: To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. PATIENTS AND METHODS: A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. RESULTS: Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 µg mg(-1). Thirteen patients responded to the treatment. CONCLUSIONS: Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history.

Thiazolidinedione derivatives as novel agents against Propionibacterium acnes biofilms.

AIMS: The aim of the present study was to determine the effect of two thiazolidinedione derivatives on Propionibacterium acnes biofilm formation in vitro and to assess their effect on the susceptibility of P. acnes biofilms towards antimicrobials. METHODS AND RESULTS: The compounds were shown to have a moderate to strong antibiofilm activity when used in subinhibitory concentrations. These compounds do not affect P. acnes attachment but lead to increased dispersal of biofilm cells. This dispersal results in an increased killing of the P. acnes biofilm cells by conventional antimicrobials. CONCLUSION: The antibiofilm effect and the effect on biofilm susceptibility of the thiazolidinedione-derived quorum sensing inhibitors were clearly demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: Propionibacterium acnes infections are difficult to treat due to the presence of biofilms at the infection site and the associated resistance towards conventional antimicrobials. Our results indicate that these thiazolidinedione derivatives can be promising leads used for the treatment of P. acnes infections and as anti-acne drugs.

Weather conditions and daylight-mediated photodynamic therapy: protoporphyrin IX-weighted daylight doses measured in six geographical locations.

BACKGROUND: Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated methyl aminolaevulinate PDT (daylight-PDT) is a simple and painless treatment procedure for PDT. All daylight-PDT studies have been performed in the Nordic countries. To be able to apply these results in other parts of the world we have to compare the daily protoporphyrin IX (PpIX) light dose in other countries with the PpIX light doses found in Nordic countries. OBJECTIVES: To calculate where and when daylight-PDT of AKs was possible in six different geographical locations using ground stations measuring PpIX-weighted daylight doses. METHODS: PpIX-weighted daylight doses were measured using a dosimeter with a customer-specific photodiode with a detector sensitivity that mimics the PpIX absorption spectrum and measures in 'PpIX doses'. The dosimeters were built into ground stations that were placed in six geographical locations measuring from July to December 2008. Temperature data for each location were obtained from the internet. The maximal ultraviolet (UV) index for Copenhagen was obtained for the measuring period of the dosimeters. RESULTS: If the PpIX light dose should be above 8Jcm(-2) and the maximum temperature of the day at least 10°C, it was possible to treat patients on nearly all days until the middle of September in Reykjavik and Oslo, until the last week of October in Copenhagen and Regensburg, until the middle of November in Turin and all year in Israel. CONCLUSIONS: Where and when to perform daylight-PDT depends on the PpIX light dose and outdoor temperature. The PpIX light dose was influenced by the geographical location (latitude), weather condition and time of year. The UV index was not more suitable than temperature and weather to predict if the intensity of daylight would be sufficient for daylight-PDT.

Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study.

BACKGROUND: Photodynamic therapy (PDT) is a highly effective treatment for actinic keratoses (AK); however, it is time consuming and often painful for the patient. Daylight-PDT would make the treatment independent of the clinic and less painful due to the continuous activation of small amounts of porphyrins during its formation. OBJECTIVES: The objective of this randomized controlled study was to compare response rates and adverse effects after methyl aminolevulinate (MAL)-PDT using conventional red light-emitting diode (LED) light vs. daylight. PATIENTS/METHODS: Twenty-nine patients with AK of the face and scalp were treated with MAL-PDT in two symmetrical areas. One area was illuminated by red LED light (37 J cm(-2)) after 3-h incubation with MAL under occlusive dressing. The other area was treated with daylight for 2.5 h after the MAL cream had been under occlusion for half an hour. RESULTS: We found no significant difference in the treatment effect between the two treatments (P = 0.13), with a reduction of AK lesions of 79% in the daylight area compared with 71% in the LED area. Treatment response in the daylight area did not depend on the intensity of the daylight. Illumination with LED was more painful than daylight (P < 0.0001). Erythema and crusting occurred after both treatments and were similar in the two areas. CONCLUSIONS: PDT of AK by continuous activation of porphyrins by daylight proved to be as effective as conventional PDT. PDT using daylight activation will make the treatment of these extremely common premalignant tumours more time and cost effective, and more convenient for the patient.

Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin-like growth factor-binding protein-7 after phototherapy.

BACKGROUND: Phototherapy is an effective therapy for psoriasis. The molecular mechanisms underlying its efficacy are not yet understood. OBJECTIVES: To compare the expression profiles of psoriatic epidermis in patients before and after undergoing phototherapy with the purpose of expounding the molecular mechanisms underlying the efficacy of this therapeutic modality. METHODS: Patients with psoriasis were investigated before and after full courses of phototherapy: three patients completed 3 weeks of heliotherapy at the Dead Sea; three patients received narrowband ultraviolet B (NB-UVB) for a total of 20-27 treatments. Epidermal samples were analysed using oligonucleotide microarrays. Our microarray results led us to explore further and to quantify a specific gene, insulin-like growth factor-binding protein-7 (IGFBP7), using real-time quantitative reverse transcriptase-polymerase chain reaction assays and immunohistochemical protein expression. RESULTS: We identified 315 genes modulated by phototherapy: the expressions of 248 genes (142 up; 106 down) were changed by Dead Sea treatment, 116 (71 up; 45 down) by NB-UVB and 49 (37 up; 12 down) were modulated regardless of treatment. The differentially changed genes include S100 calcium-binding proteins, dendritic cell markers, tumour necrosis factor-alpha target genes, matrix metalloproteinases and NFkappaB target genes. We also found that IGFBP7 mRNA and protein were significantly underexpressed in psoriatic compared with normal epidermis, and that phototherapy significantly increased their expression. CONCLUSIONS: IGFBP7 is underexpressed in psoriatic epidermis but is inducible by UVB.

The UVB-induced gene expression profile of human epidermis in vivo is different from that of cultured keratinocytes.

In order to obtain a comprehensive picture of the molecular events regulating cutaneous photodamage of intact human epidermis, suction blister roofs obtained after a single dose of in vivo ultraviolet (UV)B exposure were used for microarray profiling. We found a changed expression of 619 genes. Half of the UVB-regulated genes had returned to pre-exposure baseline levels at 72 h, underscoring the transient character of the molecular cutaneous UVB response. Of special interest was our finding that several of the central p53 target genes remained unaffected following UVB exposure in spite of p53 protein accumulation. We next compared the in vivo expression profiles of epidermal sheets to that of cultured human epidermal keratinocytes exposed to UVB in vitro. We found 1931 genes that differed in their expression profiles between the two groups. The expression profile in intact epidemis was geared mainly towards DNA repair, whereas cultured keratinocytes responded predominantly by activating genes associated with cell-cycle arrest and apoptosis. These differences in expression profiles might reflect differences between mature differentiating keratinocytes in the suprabasal epidermal layers versus exponentially proliferating keratinocytes in cell culture. Our findings show that extreme care should be taken when extrapolating from findings based on keratinocyte cultures to changes in intact epidermis.

Photoprotection by Cichorum endivia extracts: prevention of UVB-induced erythema, pyrimidine dimer formation and IL-6 expression.

In the gradual process of evolution, plants have developed natural sun protecting substances that enable continuous survival under direct and intense ultraviolet (UV) radiation. As part of our studies of plant-derived pigments that might constitute an alternative to conventional sunscreens, we have tested the ethanolic extracts of roots, stalks, and inflorescences of populations of wild Cichorum endivia subsp. Divaricatum (Asteraceae) in terms of protection against sunburn, and in prevention of UVB-induced pyrimidine dimer formation and IL-6 mRNA expression in the human keratinocyte cell line, HaCaT. Using ELISA technique for detection of pyrimidine dimers and RT-PCR for detection of IL-6, we found that the ethanolic extract of C. endivia roots absorbs radiation in the UVB spectrum and partially prevents induction of pyrimidine dimers and IL-6 expression. Application of the root extract on the skin prior to UVB irradiation totally prevented erythema. Our findings suggest that C. endivia extracts might possess sun-protective qualities that make them useful as sunscreens.

[Cutaneous leishmaniasis]. / Kutane Leishmaniose.

Leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoa, Leishmania, which resides in macrophages. The parasite is transmitted by an infected female sandfly. The incidence of cutaneous leishmaniasis approaches 2 million new cases per year with 90% of the cases occurring in the "Old World", while the "New World" accounts for the rest. Infection may be restricted to the skin with development of characteristic ulcers, or may affect the mucous membranes in its mucocutaneous form. The clinical diagnosis is verified by the presence of amastigotes in slit-skin smears. Therapeutic modalities include systemic treatments such as the pentavalent antimony compound sodium stibogluconate, liposomal formulations of amphotericin B, oral ketoconazole or itraconazole, as well as topical paromomycin sulphate, local heat, freezing with liquid nitrogen, or photodynamic therapy. An effective vaccine is not available.

[Onchocerciasis]. / Onchozerkose.

Onchocerciasis is an infestation caused by the nematode, Onchocerca volvulus, and characterized by eye manifestations, skin lesions and troublesome itching. Although partially controlled by international mass treatment programs, onchocerciasis remains a major health hazard in endemic areas in Africa, Arabia, and the Americas. Onchocerciasis is spread by bites from infested blackflies which transmit larvae that subsequently develop into adult filariae. Skin findings are commonly non-specific, and include severe pruritus, acute and chronic dermatitis, vitiligo-like hypopigmentation and atrophy. Onchocercal ocular disease has a large spectrum of manifestations and may even lead to blindness. Diagnosis is usually made by direct visualization of the larvae emerging from superficial skin biopsies, "skin snips". In some cases, the microfilariae can also be directly observed with a slit lamp when they migrate into the anterior chamber of the eye. Ivermectin is highly microfilaricidal, and is the current drug of choice for both skin and ocular manifestations.

Expression of tyrosinase, MIA and MART-1 in sentinel lymph nodes of patients with malignant melanoma.

BACKGROUND: Regional lymph node status is an important predictor of survival in patients with malignant melanoma. Mapping of sentinel lymph nodes using sensitive molecular techniques has recently been introduced. Malignant melanoma is heterogeneous in terms of its biological, immunological and metastatic properties, and melanoma cells exhibit a polymorphous expression of tumour markers. Thus, assays that include multiple markers appear to be more sensitive than single-marker assays. OBJECTIVES: To characterize the molecular profiles of melanoma cells in sentinel lymph nodes employing the mRNA expression of tyrosinase, MIA and MART-1 as markers. METHODS: Samples of sentinel lymph nodes from 17 melanoma patients and 18 control nodes from non-melanoma patients were assayed by reverse transcriptase-polymerase chain reaction, using specific primers for each marker. RESULTS: We found that both tyrosinase and MIA expression were sensitive indicators of micrometastases in sentinel lymph nodes that were negative on routine histopathological examination, and that the finding of micrometastases expressing MART-1 in sentinel lymph nodes was negatively correlated with overall survival. CONCLUSIONS: Characterization of the molecular profiles of melanoma cells constitutes a valid means of detecting metastatic melanoma cells in sentinel lymph nodes, and of predicting the survival of melanoma patients.

Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population.

The aim of this study was to examine whether the association of psoriatic arthritis (PsA) with human leukocyte antigen (HLA) class I genes is secondary to linkage disequilibrium with a nearby gene. We examined a sample of the Jewish population to investigate whether HLA-B/C and DR polymorphism is associated with susceptibility, or whether other closely related class I loci, such as the major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor (TNF), might play a role in disease development. Comparisons of different populations with different HLA profiles would be of value in identifying the candidate genes involved in PSA. Fifty-two patients with PsA and 73 random matched controls from a Jewish population were selected and DNA typed by polymerase chain reaction-single-strand oligonucleotide probe (PCR-SSOP) (HLA-C), PCR sequence-specific primers (PCR-SSP) (HLA-B, -DR), radioactive PCR (MICA-TM polymorphism in the transmembrane region), and PCR-RFLP (TNF). Some findings can be concluded from the study: (1) the frequency of HLA-B*5701, B*3801, B*39, B*27, Cw*0602, Cw*07, DRB1*0402, and DRB1*0701 were not found to be significantly increased in PsA; (2) no significant differences of TNFalpha promoter alleles at positions -308 and -238 were found between PsA and healthy controls; (3) the trinucleotide repeat polymorphism MICA-A9 was present at a higher frequency in PsA patients, (p(c) < 0.009, RR = 3.34, EF = 0.39); and (4) MICA-A9 polymorphism was found in linkage disequilibrium with HLA-B alleles (B*5701, B*3801) described to be associated with PsA in Caucasians. These results suggest that the MICA gene or other nearby gene(s) may be involved in the development of PsA, and it would thus appear that psoriasis vulgaris (PsV) and PsA are associated with different MHC susceptibility genes.

Partial protection against epidermal IL-10 transcription and Langerhans cell depletion by sunscreens after exposure of human skin to UVB.

Sunscreens capable of inhibiting erythema are assumed to protect against UV-induced carcinogenesis as well. However, the correlation between inflammation and carcinogenesis is uncertain, and the prevention of UV-induced erythema might in fact be biologically irrelevant as an indicator of protection against UV-induced skin cancer. Ultraviolet-B radiation promotes cutaneous immunosuppression by the release of immunoregulatory cytokines and by depletion of Langerhans cells. We investigated the ability of two different sunscreens to inhibit UVB-induced expression of epidermal interleukin (IL)-10 and depletion of Langerhans cells. Chemical and physical sunscreens were applied to the forearms of volunteers 15 min prior to 4 minimal erythemal doses of UVB exposure. Suction blisters were induced 24 h after irradiation, and RNA was extracted from the blister roofs. Reverse transcription polymerase chain reaction was performed using primers for IL-10 and CD1a. A chemical sunscreen containing octyl methoxycinnamate (12 sun protection factor [SPF]) and a physical sunscreen containing zinc oxide (16 SPF) were assayed: UVB-induced IL-10 mRNA expression was nearly totally inhibited by both sunscreens (median protection for chemical and physical sunscreens was 95% and 78%, respectively), whereas UVB-induced Langerhans cell depletion was partially prevented (47% and 50% for chemical and physical sunscreens, respectively). Langerhans cell protection by sunscreens was confirmed by estimation of cell density after ATPase staining. In contrast, both sunscreens effectively prevented the induction of UVB-induced erythema. We believe this to be the first demonstration that sunscreens can prevent the induction of cutaneous mediators of immunosuppression, and that the results indicate that the immunoprotection offered by the sunscreens is significantly lower than their ability to prevent erythema.

Ultraviolet B irradiation: a new therapeutic concept for the management of oral manifestations of graft-versus-host disease.

Ultraviolet irradiation inhibits the proliferative responses of lymphoid cells to mitogens and alloantigens by inactivation of T lymphocytes and antigen-presenting cells. Its immunosuppressive capacity led to the introduction of UV irradiation into clinical practice for the treatment of dermatologic manifestations of chronic graft-versus-host disease. The cumulative experience with psoralen-UV-A rays in the treatment of cutaneous and oral graft-versus-host disease was the incentive for the application of oral UV-B rays in 2 patients with oral graft-versus-host disease signs and symptoms after allogeneic marrow transplantation. Intraoral UV-B irradiation (0.02 mJ/cm(2)) was administered 2 or 3 times per week on an ambulatory basis; the dose was increased by 0. 02 mJ/cm(2) every fourth session. Both patients responded early and satisfactorily, displaying only minimal side effects at a relatively low cumulative dose. Intraoral UV-B proved a valuable modality in the treatment of resistant chronic oral graft-versus-host disease.

Chronic graft-versus-host disease treated with UVB phototherapy.

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation. Immunosuppressive treatment regimens carry the potential of causing severe morbidity and mortality, so that additional modes of therapy with fewer side-effects are clearly needed. Five cGVHD patients (sclerodermoid cGVHD in two patients, lichenoid cGVHD in one patient and intraoral cGVHD in two patients), who had not responded to standard immunosuppressive drugs, were treated with adjuvant UVB phototherapy. The patient with lichenoid cGVHD experienced complete clearing of cutaneous lesions, whereas both patients with sclerodermoid cGVHD experienced significant relief of pruritus, but showed no change of the sclerodermoid skin lesions. Intraoral lesions cleared in one patient. The effects of UVB phototherapy were furthermore documented by measurement of skin viscoelasticity and mouth opening. No side-effects were encountered. This preliminary study suggests that UVB phototherapy is useful as an adjuvant therapeutic modality in intraoral and cutaneous lichenoid cGVHD.

UVB induces IL-12 transcription in human keratinocytes in vivo and in vitro.

Human epidermal cells produce a wide range of cytokines, including those characteristic of Th2-like responses such as interleukin (IL)-4 and IL-10. As well, keratinocytes have recently been shown to produce Th1-like cytokines such as IL-12. Exposure to UVB has profound effects on the skin and systemic immune system, which is in part mediated by secretion of tumor necrosis factor (TNF)-alpha by epidermal cells. Because IL-12 induces production of TNF-alpha by certain cells of the immune system, we sought to determine whether UVB is an inducer of IL-12 gene expression in epidermal cells. Human epidermal cells were exposed to UVB radiation in vivo, isolated by suction blister technique and trypsinization and transcription of the IL-12 p35 and p40 chains was examined by RT-PCR. We found the p35 chain of IL-12 to be constitutively expressed and the p40 chain inducible by UVB irradiation. Because epidermis consists of a heterogenous cell population with distinct cytokine repertoires, we sought to determine the cellular source of the IL-12 message after UVB exposure. After depleting UVB-exposed epidermal cells for DR+ cells, no reduction in the IL-12 activity was detected, suggesting that keratinocytes are a source of IL-12 transcripts in UVB-exposed human epidermis. This was supported by the up-regulation of IL-12 p40 transcripts in UV-irradiated cultured keratinocytes that were devoid of DR+ cells. Up-regulation of IL-12 p40 gene expression by UVB as demonstrated here, taken together with the finding that keratinocytes also up-regulate IL-10 transcription, suggests that there is a complex interplay between Th1- and Th2-like epidermis-derived cytokines following exposure to UVB.