Effects of Systemic Interleukin-10 Therapy on Psoriatic Skin Lesions: Histologic, Immunohistologic, and Molecular Biology Findings

Abstract

Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin 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. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase-polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards 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 interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10.

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

“…Exemplary, the CXCR2 ligand CXCL8 (IL-8), as a major neutrophilrecruiting and -activating factor, is found to be diminished in vitro also without prior stimulation by LPS and can be confirmed also in vivo (Table 1) [19].…”

Circulating monocytes in patients with acute coronary syndromes lack sufficient interleukin-10 production after lipopolysaccharide stimulation

“…It inhibits a broad array of inflammatory processes such as T helper Type I cell (proinflammatory) cytokine production, antigen presentation and antigen-specific T cell proliferation [20,21]. It is demonstrated that IL-10 decreases inflammatory activity in vivo, as shown in T helper Type I mediated diseases such as psoriasis [22].…”

Interleukin-10 Therapy—Review of a New Approach

“…The physiological significance of these findings was reflected by the depressed DTH reaction to recall antigens during IL-10 therapy (Asadullah et al, 1999a). 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 effect (Asadullah et al, 2001b;Reich et al, 2001). Direct effects of IL-10 on keratinocytes are unlikely to have contributed to the clinical response, since the IL-10 unresponsiveness of keratinocytes has been demonstrated by us recently (see above).…”