Psoriasis. Leukocytes and cytokines.
Elements of the immune system must take their place alongside other potential mechanisms of psoriasis, such as psoriatic epidermal keratinocytic hyperproliferation, endothelial cell and fibroblast activation and proliferation, abnormal lipid regulation, and transmembrane signalling abnormalities. These data provide support for the concept that cellular immunologic processes are active in a manner that further promotes the patho-physiologic events observed in psoriasis. Thus, therapies useful for psoriasis may have activity on immunologic processes in addition to more traditional mechanistic conceptions of effects on keratinocyte proliferation or other constitutive cell activity. As depicted in Figure 1, UV light, steroids, cyclosporine, and tars have potent inhibitory effects on antigen-presenting cells as well as on T cells. Methotrexate and azathioprine both have immunosuppressive activities, and even retinoids have complex immunomodulatory activity in addition to their ability to alter keratinocyte differentiation (or responsiveness to lymphokines). Cyclosporine has potent effects on T cells after they encounter activating signals such as foreign antigens or autoantigens. Although the T cell actually can become partially activated in the presence of cyclosporine, the drug interferes with the ability of the activated T cell to synthesize and secrete lymphokines (such as IL-2 or gamma-interferon) critical for the initiation and amplification of immune responses to a particular antigen. Although interruption of a single critical pathway improves psoriasis, it is likely that the most effective medications for psoriasis have actions on more than one cell type important in the pathogenesis of the lesion.
Cooper
K D
KD
Department of Dermatology, University of Michigan, Ann Arbor.
D002455:Cell Division; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008213:Lymphocyte Activation; D011565:Psoriasis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines