Immunomodulatory Effects of Vitamin D Analogues in Psoriatic Skin

Bezanis, Gregory J; Choi, Jee Ho; Kang, Se Won

Abstract

Psoriasis is an inflammatory skin disease characterized by hyperproliferation and incomplete differentiation of keratinocytes. Mounting scientific evidence suggests that this epidermal alteration occurs as a response to an immunologic injury, giving rise to the concept that psoriasis is a skin-specific autoimmune disease. Indeed, many effective therapeutic agents for psoriasis are immunosuppressive in nature, lending further support to this view. The well known ability of calcipotriene and 1,25(OH)2D3 to inhibit keratinocyte proliferation and to induce its differentiation is certainly compatible with their antipsoriatic actions. In addition, topical calcipotriene has been shown to correct, at least in part, the local cytokine imbalance observed in psoriatic lesions. Interleukin (IL)-8 is a proinflammatory cytokine that is chemotactic for polymorphonuclear cells and T lymphocytes. It also promotes proliferation of keratinocytes and endothelial cells. In lesional psoriatic skin, IL-8 and its receptor levels are markedly elevated. IL-10 is an immunosuppressive cytokine, which as a type2 (T2) cytokine antagonizes cell-mediated immunity. Indeed, IL-10 administration has been shown to improve psoriasis. Topical calcipotriene markedly reduces elevated levels of IL-8 while simultaneously increasing IL-10 levels in lesional skin of psoriasis. These changes occur very early, within the first three days of therapy, prior to significant clinical improvement of psoriasis, indicating that the cytokine alterations are not simply secondary to resolution of psoriatic plaques. Therefore, elaboration of the immunosuppressive cytokine IL-10 and a concomitant reduction in the proinflammatory cytokine IL-8 may mediate the immunopharmacological improvementin psoriasis by calcipotriene.