Dr. med. Wolf-Dietrich Döcke

Interleukin-10 and psoriasis

Schering AG, Berlin

Interleukin (IL)-10 is an important immunoregulatory cytokine produced by many cell populations. It plays an outstanding role in several immune reactions including regulatory mechanisms in the skin. We found a relative deficiency in cutaneous IL 10 expression in psoriasis1, which might have a genetic background2. Several lines of evidences suggested that IL 10 may have antipsoriatic capacity. Therefore we performed 3 clinical trials with IL-10. In one pilot1 and a phase-2 trial 3 with subcutaneous IL 10 administration over 3-7 weeks in patients with established severe psoriasis, the cytokine was well tolerated. Clinical efficiency was found in the majority of patients, which was confirmed by histological and immunohistochemical investigations. In a placebo-controlled, double-blind, phase II long term trial in patients with chronic plaque psoriasis in remission, IL-10 therapy decreased the incidence of relapse and prolonged the disease free interval4. It is likely that IL 10 exerts its antipsoriatic activity by effects on different cell populations including T cells and APCs as well as their mutual interaction. We observed depressed monocytic HLA DR and CD86 expression as well as TNF-alpha and IL-12 secretion capacities during IL-10 therapy. Moreover, IL 10 led to a lasting type 1/ type 2 shift (increasing proportion of IL 4, IL 5, and IL 10 producing T cells, selective increase in IgE serum levels)1. A negative correlation was demonstrated between the IL-4 secretion capacity and Psoriasis Area and Severity Index score was found in our long term trial4. The physiological significance of these findings was reflected by the depressed DTH reaction to recall antigens during IL-10 therapy3. Interestingly, IL-10 therapy led to a decrease in cutaneous IL-8 and an increase in IL-4 expression, both of which might contribute to the antipsoriatic effect5. Direct effects of IL 10 on keratinocytes, however, are unlikely to have contributed to the clinical response, since we demonstrated the IL-10 unresponsiveness of keratinocytes in vitro6. IL-10 therapy seems to be well tolerated and immunologically effective in psoriasis. To determine definitive clinical efficacy, however, awaits phase III studies.

References:
1. Asadullah et al.: IL-10 is a key cytokine in psoriasis: Proof of principle by IL-10 therapy - a new therapeutic approach, J Clin Invest, 101:783-794, 1998
2. Asadullah K et al.: Interleukin-10 promotor polymorphism in psoriasis, J Invest Dermatol, 116:975-8., 2001
3. Asadullah K et al.: IL-10 treatment of psoriasis - clinical results of a Phase II trial, Arch Dermatol , 135: 187-192, 1999
4. Friedrich et al.: Immunomodulation by IL 10 therapy decreases the incidence of relapse and prolongs the relapse-free interval in psoriasis. J Invest Dermatol, 118:672-677 , 2002
5. Asadullah K et al.: Effects of systemic interleukin-10 therapy on psoriatic skin lesions: histological, immunohistological and molecularbiological findings, J Invest Dermatol 116:721-7, 2001
6. Seifert et al.: The antipsoriatic activity of IL-10 is rather caused by effects on peripheral blood cells than by direct effect on human keratinocytes, Arch Derm Res, 292:164-172, 2000

Prof. Dr. med. Wolf-Dietrich Döcke

Fotos: GD Gesellschaft für Dermopharmazie

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