Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. In 14 patients, an area of psoriasis and adjacent uninvolved skin were exposed to a series of UVA doses (350 ± 30 nm, 1–16 J/cm²), using an irradiation monochromator. Six other patients were similarly phototested with a series of UVB doses (300 ± 5 nm, 20–112 mJ/cm²) to both uninvolved and lesional skin. Erythema was judged visually at 72 h for psoralen–UVA, and at 24 h for UVB, and measured using a scanning laser–Doppler velocimeter. In 10 patients, PUVA therapy using high-dose UVA was subsequently given to lesional skin (8–16 J/cm² twice weekly) in addition to conventional whole-body PUVA. For psoralen–UVA, the minimal phototoxic dose within psoriasis was increased by a factor of 4 compared with non-lesional skin (P < 0.01, Wilcoxon signed-rank test). For UVB, the minimal erythema dose within psoriasis was higher than that for non-lesional skin (medians > 112 and 28 respectively, P < 0.05). Laser–Doppler measurements confirmed that the reduced erythemal sensitivity was not due to masking of response by pre-existing increased blood flux within psoriasis. In six patients, the sites subsequently treated twice weekly with PUVA, using high-dose UVA, cleared faster (median number of treatments 3), but with a similar cumulative UVA dose, compared with adjacent lesional skin treated with conventional PUVA (median number of treatments 12). This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease.     

Langerhans' cells in patients with psoriasis: effect of treatment with PUVA, PUVA bath, etretinate and anthralin

Suction blisters were raised in lesions and normal appearing skin of patients with psoriasis. The blister roof which contains the epidermis separated at the dermal-epidermal junction was stained with ATPase, OKT-6 and anti-HLA-DR monoclonal antibodies. The technique permits the counting of the Langerhans' cells per mm2. Their mean number varied between 888-987 cells per mm2 in control subjects with the three staining procedures. In patients with psoriasis, the number of cells before treatment was between 1110-1179 in uninvolved skin and 521-1001 per mm2 in the lesions as measured using both monoclonal antibodies and ATPase. However, the latter technique seemed to be inappropriate for lesional skin. After treatment with PUVA bath or oral PUVA with or without etretinate, fewer Langerhans' cells were seen in both lesions and normal appearing skin with the appearance of giant Langerhans' cells with long dendrites. In patients healed with anthralin + UV-B the Langerhans' cells appeared normal in number and size.     

The usefulness of reflectance spectrophotometric measurements during psoralens and ultraviolet A therapy for psoriasis

Reflectance spectrophotometry was used to obtain indices of the hemoglobin and melanin content of psoriatic lesions and adjacent clinically normal skin in thirteen patients undergoing photochemotherapy. The pretreatment lesional hemoglobin index was 2.8 times greater than that of adjacent uninvolved skin. With therapy, this index decreased rapidly initially, and during the second or third week approached that of the uninvolved skin. The ratio of lesional and uninvolved skin hemoglobin indices decreased to approximately 1.3, and continuation of PUVA treatment failed to reduce it further. Termination of treatment at this stage, which occurs before clinical resolution, resulted in subsequent clearance of psoriasis. The decrease in the lesional hemoglobin index and the clearance time appeared to be dose-dependent, and, indeed, a more aggressive regimen resulted in approximately 50% reduction in both the number of treatments and the cumulative dose required to achieve a stable hemoglobin index ratio and subsequent clinical clearance.     

In situ expression of messenger RNA of interleukin-1 and interleukin-6 in psoriasis: interleukin-6 involved in formation of psoriatic lesions

Summary Psoriasis is a disease of abnormal proliferation and differentiation of epidermal cells. Several cytokines released by keratinocytes are implicated as factors responsible for this pathological condition of the epidermis. In order to elucidate the role of these cytokines in psoriasis, messenger RNA (mRNA) expression of interleukin-1 (IL-1) and IL-6 in psoriatic epidermis was investigated using biotin-labelled complementary DNA (cDNA) of the cytokines. Messenger RNA of IL-1 was weakly detected in some normal healthy epidermis specimens and more strongly in all the perilesional uninvolved psoriatic epidermis specimens. It was also expressed in the transitional zone between uninvolved and fully developed psoriatic skin, but was not expressed in lesional skin. In contrast, IL-6 mRNA was rarely expressed in normal healthy epidermis, but was expressed in perilesional uninvolved psoriatic epidermis, in the transitional zone and in the fully developed lesional epidermis, with the maximum intensity in the transitional zone. Expression of mRNA of IL-6 receptor showed a similar tendency to that of IL-6. It was expressed in psoriatic epidermis, most strongly in the transitional zone, but not in normal healthy epidermis. IL-6 was demonstrated immunohistochemically in psoriatic epidermis, but IL-6 receptor was demonstrated only in the transitional zone. Thus IL-6 and its receptor expression correlated well with the formation of psoriatic lesions where IL-1 may initiate their expression. IL-6 may play an important role in the pathogenesis of psoriasis.     

Distribution of interleukin 1 receptor antagonist protein (IRAP), interleukin 1 receptor, and interleukin 1α in normal and psoriatic skin. Decreased expression of IRAP in psoriatic lesional epidermis

The distribution of interleukin 1 alpha (IL-1 alpha), type 1 interleukin 1 receptor (IL-1R), and the interleukin 1 receptor antagonist protein (IRAP), was investigated in biopsies of normal skin, and in uninvolved and lesional skin of patients with psoriasis, using specific monoclonal antibodies. We report the novel finding that IRAP is distributed throughout the living layers of the epidermis in normal skin, and is also associated with sebaceous glands and eccrine sweat glands. Our finding that the inhibitor protein IRAP is present in areas where the pro-inflammatory cytokine IL-1 alpha is distributed provides strong evidence in favour of a cytokine regulatory system in normal skin. We further document for the first time that IL-1R in normal skin is localized to the living layers of the epidermis, sebaceous and eccrine glands, as well as to a prominent network of dermal dendritic cells, and upper dermal blood vessels. There was a consistent reduction in the level of IRAP expression in lesional compared with uninvolved skin in biopsies from six out of seven psoriasis patients. Decreased IRAP expression in lesions of psoriasis indicates that alterations in the level of this inhibitor protein may be important in the pathogenesis of inflammatory skin conditions.     

Expression of interleukin-6-like molecules and tumour necrosis factor after topical treatment of psoriasis with a new vitamin D analogue (MC 903)

Skin biopsies from 5 patients with chronic plaque psoriasis were examined to test the effect of topical treatment with a new synthetic vitamin D3 analogue, MC 903, on epidermal interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF alpha). Skin biopsies, taken before therapy and after one and 2 weeks of therapy were examined immunohistologically. IL-6 was visualized using a partially purified polyclonal antiserum to crude supernatants of activated human blood monocytes before and after absorption with recombinant human IL-6. TNF alpha was demonstrated using a specific polyclonal antiserum to human recombinant TNF alpha. Both the intensity and extension of staining for IL-6, but not for TNF alpha, were increased in lesions compared with unaffected skin. During therapy with MC 903 a decline in the staining intensity for IL-6, but not for TNF alpha, was observed in both lesional and unaffected skin. Placebo-treated lesions, however, remained unchanged.     

银屑病皮损区和非皮损区AgNOR的定量观察

应用核仁组成区银染蛋白（ＡｇＮＯＲ）染色方法，对１２例银屑病患者皮损区和非皮损区表皮细胞进行了观察。并和非银屑病患考的正常皮肤及慢性皮炎类皮损各１２例进行了比较。结果显示银屑病患者皮损区和非皮损区ＡｇＮＯＲ值均数均明显高于正常皮肤和慢性皮炎类皮损，而后两者相类似。作者认为ＡｇＮＯＲ在组织学上可能有助于银屑病和一些慢性皮炎类疾病的鉴别。     

Turbo-PUVA: dihydroxyacetone-enhanced photochemotherapy for psoriasis: a pilot study.

BACKGROUND: Dihydroxyacetone (DHA), a colorless sugar in "sunless" tanning lotions, binds to stratum corneum to form a UV-A-protective brown pigment. Bound DHA polymer is shed faster from hyperproliferative skin sites such as psoriatic plaques. We tested the hypothesis that selective shedding of DHA pigment during psoralen-UV-A (PUVA) treatment of psoriasis may allow higher UV-A doses, thus accelerating clearing while protecting uninvolved skin. Concurrent use of lactic acid was investigated as an aid in removing scale and residual DHA from psoriatic plaques. OBSERVATIONS: Thirty psoriatic patients with more than 20% body surface area involvement were recruited. The 6 PUVA study groups were (1) standard American style, (2) American style plus lactic acid, (3) DHA-PUVA or "topical ultraviolet-resisting barrier to optiimize PUVA" (Turbo-PUVA), (4) Turbo-PUVA with lactic acid, (5) European style, and (6) European style plus DHA. Combinations of lactic acid and European-style treatment were not studied. Each subject received up to 30 oral PUVA treatments twice weekly 3 days apart. The DHA-PUVA groups used 15% DHA lotion twice weekly. Lactic acid groups used 7% lotion daily except on treatment days. Psoriasis area and severity index scores were recorded weekly. Turbo-PUVA allowed higher UV-A exposures with minimal burns, showed faster clearing, and required fewer treatments for 90% clearing (P<.001). CONCLUSIONS: Protection of uninvolved skin by DHA during PUVA treatment allows higher UV-A exposures to be tolerated, demonstrates faster clearing, and requires fewer treatments to clear psoriasis. By reducing the total body dose received, Turbo-PUVA may also reduce long-term risks.     

Phototherapy of urticaria pigmentosa: Clinical response and changes of cutaneous reactivity,histamine and chemotactic leukotrienes

Summary Ten patients with moderate to very severe urticaria pigmentosa were studied for the therapeutic effect of photochemotherapy (PUVA; six adults) and selective ultraviolet phototherapy (SUP; four adolescents). Despite a high mean PUVA dosage (138.6 ±63.4 J/cm²), only two patients had a very good response, while three had a good response and one had a fair response. On the reduction of the frequency of treatments, the symptoms gradually recurred, and several months after the discontinuation of therapy, the clinical status had reached the level prior to PUVA. The results with SUP were even less encouraging. A number of biophysical and biochemical parameters of the skin were studied in five patients before PUVA treatment, immediately after several months of PUVA treatment and again 5 months after the discontinuation of PUVA treatment. Weal and erythema reactions to intracutaneous skin tests remained unchanged after PUVA, while wealing with topically applied dimethylsulfoxide (DMSO) decreased. Transepidermal water loss was markedly reduced over DMSO weals. Histamine levels, which were elevated in lesional but not in normal skin, dropped with PUVA treatment, but after the discontinuation of treatment, they increased again in the lesions. On reverse-phase high-performance liquid chromatography, two main chemotactic factors, leukotriene B₄ and 5-HETE, were identified in lesional skin. Chemotactic activity was elevated in both lesional and uninvolved patient skin, reached normal levels at both sites after PUVA and maintained these low levels for several months after the discontinuation of treatment. Our data suggest that PUVA has reversible anti-inflammatory effects on human skin, because it increases epidermal-barrier function and decreases the synthesis of mediators of inflammation. These observations show the transitory therapeutic benefit of PUVA in patients with urticaria pigmentosa.     

Lack of evidence for activation of the hedgehog pathway in psoriasis

Recent reports have suggested that the hedgehog (Hh) pathway is activated in lesional psoriatic skin, and that treatment with the Hh pathway antagonist cyclopamine may lead to rapid resolution of the disease. To assess Hh pathway activity in psoriasis, we isolated RNA from lesional and uninvolved skin of 58 psoriatic patients, and from 63 normal control subjects, and subjected these samples to global gene expression profiling on Affymetrix HU133 Plus 2.0 gene arrays. We were especially interested in Hh target genes (PTCH1 and GLI1), whose expression is elevated in response to Hh signaling. The microarray data demonstrated downregulation of PTCH1 expression in uninvolved and lesional skin (1.1-fold and 2-fold, respectively; P<0.0001). Additionally GLI1 mRNA was downregulated in lesional skin (1.7 fold; P<0.05). No significant changes were observed between lesional and uninvolved skin for the Hh ligands or Smoothened. Quantitative PCR confirmed these findings. In situ hybridization for GLI1 and PTCH1 was positive in basal cell carcinoma tumor cells, but was negligible in uninvolved or lesional psoriatic skin. The absence of elevated Hh target gene expression in lesional psoriatic skin indicates that the Hh pathway is not activated in this disease, raising questions regarding the proposed use of Hh antagonists as antipsoriatic agents.     

Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis.

Previous studies have shown that neutrophil-activating peptide 1/interleukin-8 (IL-8) is present in psoriatic scales and to a lesser extent in normal human epidermis. A panel of monoclonal antibodies and polyclonal antisera raised against IL-8 was used to localize IL-8 with immunoperoxidase techniques in non-lesional and lesional skin of patients with psoriasis and palmo-plantar pustulosis (PPP), and in corresponding sites from healthy subjects. Intracellular IL-8 immunoreactivity was found in all epidermal cell layers in biopsies of healthy subjects and in non-lesional and lesional skin in both PPP and psoriasis. The most intense immunolabeling was regularly found in the basal cell layer. Intercellular epidermal IL-8 immunolabeling was regularly detected in lesional biopsies in PPP and psoriasis, but not in healthy subjects or non-lesional skin in PPP and psoriasis. No intercellular immunolabeling was detected after successful treatment of lesional skin. The majority of cells along the eccrine sweat glands, dermal mononuclear cell infiltrates, and endothelial cells were IL-8 immunoreactive in all biopsies studied. The present study suggests that IL-8, its precursor form, or, alternatively, a degradation product is present in normal human epidermis.     

Downregulation and altered spatial pattern of caveolin-1 in chronic plaque psoriasis

BACKGROUND: Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. OBJECTIVES: To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. METHODS: Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. RESULTS: In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P < 0.002 for retrospective archival study and P < 0.01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P > 0.05). CONCLUSIONS: The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.     

PUVA irradiation restores altered binding patterns of lectins in psoriatic epidermis

We examined a series of biopsy specimens obtained from lesional skin in five psoriatic patients receiving topical PUVA treatment to see the effect of PUVA on epidermal cell membrane glycoconjugates by fluorescent staining techniques using lectins as surface markers. In psoriatic epidermis, Ulex europaeus agglutinin and Concanavalin A depicted only cytoplasmic patterns and did not show the plasma membrane fluorescence that was normally seen in nonpsoriatic skin. Following PUVA treatment, these altered staining patterns gradually normalized, with the appearance of the plasma membrane fluorescence. Restoration of the membrane staining tended to precede improvement in clinical and histologic features of psoriasis, suggesting that normalization of the altered profiles of membrane glycoconjugates is one of the beneficial effects of PUVA irradiation on psoriatic epidermis.     

Insulin‐like growth factor‐1 in psoriatic plaques treated with PUVA and methotrexate

Background The pathogenesis of psoriasis is thought to depend on the activation of immune cells and their secreted cytokines, chemokines and growth factors like IGF‐1 which may contribute to the epidermal hyperplasia of psoriasis. Treatment of psoriasis with PUVA and methotrexate are associated with clinical improvement and decrease in epidermal hyperplasia. Objective To examine the effects of PUVA and methotrexate therapy on IGF‐1 expression in psoriatic plaques and whether this change correlates with clinical response. Methods For 24 psoriatic patients, the PASI score and levels of lesional IGF‐1 and its mRNA were determined by RT‐PCR before and after treatment with either methotrexate or PUVA. Skin biopsies from 12 healthy volunteers served as control for IGF‐1 levels in normal skin. Results Lesional skin of psoriatic patients showed a statistically significant elevation in IGF‐1 and its mRNA levels in comparison to control (P = 0.0001). Both methotrexate and PUVA treatment were associated with a significant decrease in both PASI scores and lesional IGF‐1 after 10 month treatment. Conclusion Both methotrexate and PUVA therapy for psoriasis are associated with a decrease in PASI score and IGF‐1. The IGF‐1 down‐regulation may possibly be a consequence of the decrease in cytokines and inflammatory cellular infiltrate that occur following treatment with either modalities or due to their effect on local fibroblast activity and proliferation.     

Immunologic implications of PUVA therapy in psoriasis vulgaris

Summary During the combined effects of psoralen and UVA irradiation (PUVA therapy) a significant decrease (P<0.005 in T cells has been noted in 10 psoriasis patients and 10 healthy controls especially after four exposures. Based on the fact that the total number of circulating lymphocytes of the patients and the PUVA-treated healthy controls remained within the normal range, this decrease may be due to temporary physicochemical changes of the membranes of these cells but not to T cell lysis. After eight exposures these decreased T cell values returned to starting range. The starting T cell range in psoriasis patients is significantly lower (P<0.005) compared to that of healthy controls.It is of importance that before PUVA therapy in all the patients antibodies reactive with a basal cell nuclear antigen belonging to the four main Ig classes (IgM, IgD, IgE, and IgA) could be removed from the membrane of circulating lymphocytes by means of acid elution. In contrast, mainly the IgA antinuclear basal cell antibody could be eluted from circulating PMN leukocytes in the patients under investigation. After eight PUVA exposures, however, corresponding antibodies, belonging to the three main Ig classes (IgM, IgD and IgE) could also be eluted from the membranes of circulating PMN-leukocytes of the same patients. This implies an exchange of molecules during photochemotherapy. Finally, it could be shown that after effective PUVA therapy antinuclear basal cell antibodies of the psoriasis patients under study were reactive not only with the nuclei of the basal cell layer but also with almost all the nucleic of the epidermis of the uninvolved and lesional skin. The latter finding points to the fact that PUVA treatment causes at least antigenic changes of nuclear proteins in all the nuclei of the epidermis of the PUVA treated skin. Moreover, inflammatory cells with Fab fragments within the cells present in the lesional skin before PUVA disappear during this treatment.Based on a poster session presented at the occasion of the seventh joint meeting of the ESDR, Amsterdam, The Netherlands, May 1977     

Systemic photochemotherapy decreases the expression of IFN-γ, IL-12p40 and IL-23p19 in psoriatic plaques

Psoriasis vulgaris (PV) is a chronic skin disease with unclear pathogenesis. In the present study we investigated the effect of systemic photochemotherapy (PUVA therapy- psoralen and UVA therapy) on the expression of IFN-γ, IL-12p40 and IL-23p19 in lesional psoriatic skin. Fifteen patients with chronic plaque type psoriasis selected to be treated with PUVA therapy were recruited for this study. Expression of IFN-γ, IL-12p40 and IL-23p19 in psoriatic lesions before and after twenty PUVA treatments was established by using immunohistochemistry (IHC). A significant decrease in expression (p?相似文献   

Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-gamma inducers -- IL-12, IL-18 and IL-23

Type-1 cytokine-producing T cells are important in the pathogenesis of psoriasis vulgaris, for which efficient therapy is provided by means of narrow-band ultraviolet-B (NB-UVB). The expression of the type-1 cytokine interferon-gamma (IFN-gamma) is regulated by interleukin-12 (IL-12), IL-15, IL-18 and IL-23; however, not much is known about the effect of this therapy on the levels of these cytokines in lesional psoriatic skin in situ. In this study, we investigated the effects of NB-UVB therapy on the expression of IFN-gamma-inducing cytokines. Ten patients with chronic plaque-type psoriasis selected to be treated with NB-UVB therapy were recruited for these experiments and the expression of cytokines IL-12, IL-15, IL-18, IL-23 and IFN-gamma in lesional psoriatic skin before, during and after therapy was determined with the help of immunohistochemistry. Double staining was performed in order to determine the cell types expressing these cytokines. The decrease in the psoriasis area and severity index was accompanied by a significant decrease in the expression of IFN-gamma, and concomitantly, significant reduction of IFN-gamma inducers -- IL-12, IL-18 and IL-23. Thus, we concluded that the decrease of IFN-gamma expression in psoriasis lesions after NB-UVB therapy could be a result of diminished expression of IL-12, IL-18 and IL-23 in lesional skin. Therapies targeting these three cytokines should, therefore, be considered in the treatment of psoriasis.     

Blood flow in psoriatic skin lesions: the effect of treatment

Laser Doppler velocimetry (LDV) was used to assess the effect of treatment upon cutaneous blood flow in psoriatic skin lesions. The resolution of two separate plaques in each of seven subjects was followed. Six of the subjects received the Goeckerman regimen, the seventh was treated with psoralen-ultraviolet A (PUVA) therapy. Control LDV readings were taken from uninvolved skin sites during the treatment period. Cutaneous blood flow in the psoriatic lesions of the Goeckerman-treated patients decreased to levels comparable to those in uninvolved skin early in the course of treatment and significantly preceeded the observed clinical resolution from 4 to 8 days after initiation of therapy (P less than 0.05). Visible flare-ups sometimes appeared when patients were untreated (over a weekend, for example) and these eruptions were accompanied by a transient elevation of LDV readings. Perfusion of the lesions of the PUVA-treated patient remained consistently higher than perfusion of uninvolved skin despite clinical healing. In a separate series of experiments, blood flow at the extensor surface of the forearm was measured in the skin of normal subjects, the uninvolved skin of psoriatic patients and the untreated lesional skin of psoriatic patients. While the lesional skin had significantly higher perfusion levels than uninvolved psoriatic or normal control skin (P less than 0.01), there was no significant difference between blood flow to the uninvolved psoriatic skin of psoriatics and that to the skin of healthy controls.     

Effects of PUVA and mechlorethamine treatment of psoriatic patients on epidermal Langerhans' cells

Using OKT6 monoclonal antibody, we investigated the number of epidermal Langerhans' cells (LCs) in involved skin from patients with psoriasis, before and after mechlorethamine (HN2) or PUVA treatment. The number of LCs remained at about pretreatment number during three weeks of HN2 treatment alone, though they were reduced after 10 systemic PUVA treatments. Therefore, in contrast to PUVA which influences LCs, HN2 seems to have little effect on LCs. LCs in psoriatic plaques were, in number, 3-4 times less numerous than those in uninvolved, nontreated epidermis.     

Cytokine expression in psoriatic skin lesions during PUVA therapy

To determine whether an improvement in skin lesions as a result of PUVA therapy may be correlated with changes in cytokine patterns, RT-PCR amplification was used to compare the levels of IL-2, IL-6, IL-8, IL-10, TNF-α and IFN-γ cytokine mRNA expression in serial biopsies from three chronic plaque psoriatic patients. In each case, 3-mm punch biopsies were taken from lesional skin before and during 2–28 days of treatment with PUVA. Total mRNA was extracted from each biopsy, cDNA synthesized, and then amplified by 35 cycles of PCR using cytokine-specific primers. The specificity of the PCR products was confirmed by the Southern blot technique. Substantial levels of specific mRNA for each of the cytokines studied was present in the lesions prior to treatment. In two of the three patients who responded well to PUVA, a reduction in all the cytokines including IL-10 was observed compared with baseline levels. In contrast, PUVA proved to be ineffective in clearing the psoriasis of the third patient whose skin lesions worsened during the course of treatment. This was accompanied by an increase in IFN-γ but not of the other cytokines investigated, above the pretreatment level. This study showed an association between PUVA-induced resolution and decreases in the levels of various cytokines highly expressed in psoriatic lesions. Received:14 August 1995