Abstract
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.
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Aberer W, Schuler G, Stingl G, Honigsmann H, Wolff K (1981) Ultraviolet light depletes surface markers of Langerhans cells. J Invest Dermatol 76:202–210
Baker BS, Swain AF, Griffiths CEM, Leonard JN, Fry L, Valdimarsson H (1985) Epidermal T lymphocytes and dendritic cells in chronic plaque psoriasis: the effects of PUVA treatment. Clin Exp Immunol 61:526–534
Barker JNWN, Karabin GD, Stoof TJ, Sarma VJ Dixit VM, Nickoloff BJ (1991) Detection of interferon-gamma mRNA in psoriatic epidermis by polymerase chain reaction. J Dermatol Sci 2:106–111
Bjerke JE, Krogh HK, Matre R (1978) Characterisation of mononuclear cell infiltrate in psoriatic skin. J Invest Dermatol 71:340–343
Bjerke JR, Livden JK, Degre M, Matre R (1983) Interferon in suction blister fluid from psoriatic lesions. Br J Dermatol 108: 295–299
Ettehadi P, Greaves MW, Wallach D, Aderka D, Camp RDR (1994) Elevated tumour necrosis factor-alpha (TNF-alpha) biological activity in psoriatic skin lesions. Clin Exp Immunol 96: 146–151
Friedmann P (1981) Disappearance of epidermal Langerhans cells during PUVA therapy. Br J Dermatol 105:219–221
Gillitzer R, Berger R, Mielke V, Muller C, Wolff K, Stingl G (1991) Upper keratinocytes of psoriatic skin lesions express high levels of NAP/IL-8 mRNA in situ. J Invest Dermatol 97:73–79
Gommans JM, Van Hezik SJTM, Van Huystee BEWL (1987) Flow cytometric quantification of T6-positive cells in psoriatic epidermis after PUVA and methotrexate therapy. Br J Dermatol 116:661–666
Griffiths CEM, Voorhees JJ, Nickoloff BJ (1989) Characterization of intercellular adhesion molecule-1 and HLA-DR expression in normal and inflamed skin: modulation by recombinant gamma interferon and tumour necrosis factor. J Am Acad Dermatol 20:617–629
Grossmann RM, Krueger J, Yourish D, Granelli-Piperno A, Murphy DP, May LT, Kupper TS, Seghal PB, Gottlieb AB (1989) Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci USA 86:6367–6371
Issekutz TB, Stoltz JM, Van der Meide P (1988) The recruitment of lymphocytes into the skin by T cell lymphokines: the role of γ-IFN. Clin Exp Immunol 73:70–75
Kupper TS (1989) Mechanisms of cutaneous inflammation. Arch Dermatol 125:1406–1412
Moscicki RA, Morision WL, Parrish JA, Bloch KJ, Colvin RB (1982) Reduction of the fraction of circulating helper-inducer T cells identified by monoclonal antibodies in psoriatic patients treated with long-term psoralens/ultraviolet-A radiation (PUVA). J Invest Dermatol 79:205–208
Neuner P, Charvat B, Knobler R, Kirnbauer R, Schwarz A, Luger TA, Schwarz T (1994) Cytokine release by peripheral blood mononuclear cells is affected by 8-methoxypsoralen plus UV-A. Photochem Photobiol 59:182–188
Nickoloff BJ, Karabin GD, Barker JNWN, Griffiths CEM, Sarma V, Mitra RS, Elder JT, Kunkel SL, Dixit VM (1991) Cellular localization of interleukin-8 and its inducer tumour necrosis factor-alpha in psoriasis. Am J Pathol 138:129–140
Nickoloff BJ, Fivenson DP, Kunkel SL, Strieter RM, Turka LA (1994) Keratinocyte interleukin-10 expression is upregulated in tape-stripped skin, poison ivy dermatitis, and sezary syndrome, but not in psoriatic plaques. Clin Immunol Immunopathol 73: 63–68
Olaniran AK, Baker BS, Garioch JJ, Powles AV, Fry L (1995) A comparison of the stimulatory effects of cytokines on normal and psoriatic keratinocytes in vitro. Arch Dermatol Res 287: 231–236
Oxholm A, Oxholm P, Staberg B, Bendtzen K (1989) Interleukin-6 in the epidermis of patients with psoriasis before and during PUVA treatment. Acta Derm Venereol (Stockh) 69:195–199
Pang G, Couch L, Batey R, Clancy R, Cripps A (1994) GMCSF, IL-1α, IL-1β, IL-6, IL-8, IL-10, ICAM-1 and VCAM-1 gene expression and cytokine production in human duodenal fibroblasts stimulated with lipopolysaccharide, IL-1α and TNF-α. Clin Exp Immunol 96:437–443
Rivas JM, Ullrich SE (1992) Systemic supression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes: an essential role for keratinocyte-derived IL-10. J Immunol 149:3865–3871
Schlaak JF, Buslau M, Jochum W, Hermann E, Girndt M, Gallati H, Meyer zum Buschenfelde K-H, Fleischer B (1994) T cells involved in psoriasis vulgaris belong to the Th1 subset. J Invest Dermatol 102:145–149
Uyemura K, Yamamura M, Fivenson DF, Modlin RL, Nickloff BJ (1993) The cytokine network in lesional and lesional-free psoriatic skin is characterised by a T-helper type 1 cell mediated response. J Invest Dermatol 101:701–705
Valdimarsson H, Baker BS, Jonsdottir I, Fry L (1986) Psoriasis: a disease of abnormal keratinocyte proliferation induced by lymphocytes. Immunol Today 7:256–259
Yamamura M, Wang X-H, Ohmen JD, Uyemura K, Rea TH, Bloom BR, Modlin RL (1992) Cytokine patterns of immunologically mediated tissue damage. J Immunol 149:1470–1475
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Olaniran, A.K., Baker, B.S., Paige, D.G. et al. Cytokine expression in psoriatic skin lesions during PUVA therapy. Arch Dermatol Res 288, 421–425 (1996). https://doi.org/10.1007/BF02505228
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DOI: https://doi.org/10.1007/BF02505228