Effects of systemic interleukin-10 therapy on psoriatic skin lesions: Histologic, immunohistologic, and molecular biology findings

Interleukin-10 is an important anti-inflammatory and immunosuppressive cyto kine with major impact on several immune reactions, including regulatory me chanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk, The clinical re sponse suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate th e effects of systemic interleukin-10 treatment on the skin immune system, s kin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here, Histologi c examination showed a decrease of several parameters reflecting the psoria tic disease activity as acanthosis and extension of the horny layer. Immuno histologic examination demonstrated decreasing numbers of infiltrating T ce lls, dermal CD1a(+) cells, and a diminished proliferation of epidermal cell s. Using a novel, quantitative reverse transcriptase-polymerase chain react ion approach a significant shift within the cytokine pattern was found. Int erleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interl eukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, in terleukin-4 was strongly upregulated suggesting a shift from a type 1 towar ds a type 2 cytokine pattern, The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single int erleukin-10 nonresponding patient. Our findings demonstrate considerable ef fects of systemic interleukin-10 application on the skin immune systems, wh ich might contribute to the anti-psoriatic activity of interleukin-10.