[Immunomodulation using an epidermal cytokine (ETAF)]

Abstract

Tissue cultures of freshly isolated murine and human keratinocytes as well as transformed keratinocyte cell lines secret a cytokine, epidermal cell derived thymocyte activating factor (ETAF), which augments in vitro lymphoproliferative responses. Keratinocytes produce increased levels of ETAF activity after exposure to a variety of cell damaging agents such as silica, endotoxin, phorbol esters, hydroxyurea, mechanical disruption and UV-irradiation. Biochemical studies showed that ETAF is a heat- and pH-stable low molecular weight (15K) protein which is produced in low amounts and active at low (10(-10)-10(-15) M) concentration. The most important biological property of ETAF is an antigen non specific stimulation of the immunological system. ETAF in conjunction with the antigen presenting function of Langerhans cells results in an activation of T-lymphocytes and increased production of lymphokines such as Interleukin 2, which is responsible for the activation of T- and B-lymphocytes. In addition ETAF is chemotactic for polymorphonuclear leukocytes, monocytes and natural killer cells and is directly mitogenic for fibroblasts. When injected into mice ETAF induces production of acute phase proteins such as Serum Amyloid A. Furthermore ETAF may act as an endogenous pyrogen and induce fever. According to its biochemical characteristics and biological properties ETAF can not be separated from the macrophage derived Interleukin 1(IL 1), suggesting that both ETAF and IL 1 are identical. These findings indicate that production of IL 1-like molecules is not confined to cells of the immunological system and ETAF production by keratinocytes may have important implications in the pathogenesis of inflammatory as well as neoplastic skin diseases.