Treatment of psoriasis with interleukin-10.

A cutaneous immune response mediated by infiltrating T cells is a pathologic hallmark of psoriasis, and improvement of clinical symptoms has been achieved by experimental therapies using T cell-directed immunosuppressants such as anti-CD4 antibodies or the lymphocyte-selective toxin DAB389IL-2 ( Nicolas et al. 1991; Gottlieb et al. 1995). The cytokine milieu in psoriatic lesions is characterized by an increased production of proinflammatory T-helper 1 (Th1) cytokines including interleukin (IL)-2, IFN-γ, and TNF-α ( Uyemura et al. 1993). IL-10 inhibits cytokine production of Th1 cells and plays a major role in the endogenous suppression of Th1 cell-induced inflammatory responses in normal skin ( Li et al. 1994; Berg et al. 1995). In psoriatic lesions, however, counter-regulatory expression of IL-10 is weak or absent ( Nickoloff et al. 1994; Asadullah et al. 1998). Other immunosuppressive effects of IL-10 include the inhibition of dendritic cell function. Dendritic cells isolated from psoriatic lesions induce Th1-type cytokine responses in resting blood cells, and this effect is abrogated by pretreatment with exogenous IL-10 ( Mitra et al. 1995). There is also evidence that UV irradiation, an established therapy for psoriasis, modulates cutaneous inflammation by inducing production of IL-10 in keratinocytes ( Rivas & Ullrich 1992).