IL-10 is a key cytokine in psoriasis -: Proof of principle by IL-10 therapy:: A new therapeutic approach

Overexpression of proinflammatory, type 1 cytokines has been demonstrated in psoriasis and is believed to be of pathophysiological importance, IL-10 is a type 2 cytokine with major impact on immunoregulation, since it inhibits type 1/pro-inflammatory cytokine formation, Therefore, we investigated its role in psoriasis. We found a relative deficiency in cutaneous IL-10 mRNA expression compared with other inflammatory dermatoses. Interestingly, patients during established antipsoriatic therapy showed higher IL-10 mRNA expression of peripheral blood mononuclear cells than patients before therapy, This suggested that IL-10 may have antipsoriatic capacity. Therefore, we performed a phase 2 pilot trial with subcutaneous IL-10 administration (8 mu g/kg/d) over 24 d in three patients. Clinical efficiency measured by objective and subjective parameters was found, Immunosuppressive effects (depressed monocytic HLA-DR expression, TNF-alpha and IL-12 secretion capacity, IL-12 plasma levels, and responsiveness to recall antigens) as well as a shift toward a type 2 cytokine pattern (increasing proportion of IL-4, IL-5, and IL-10 producing T cells, selective increase in IgE serum levels) were observed, Remarkably, IL-10 administration also enhanced the intracutaneous IL-10 mRNA expression, Our investigations demonstrate the major importance of IL-10 in psoriasis and show that IL-10 administration represents a new therapeutic approach, This is the first report on IL-10 therapy for cutaneous disorders.