CYTOKINE NETWORKS IN THE SKIN

Whereas some cytokines, such as interleukin-1 or tumor necrosis factor-alpha, have pleiotropic biologic properties, others seem to be more restricted in their biologic behavior, Interleukin-1 and tumor necrosis factor-alpha are known to induce the tissue accumulation of a mixed leukocyte infiltrate when injected into skin, Although both cytokines alone are not chemotactic, they can induce the production of secondary leukotactic cytokines in cells and therefore represent primary cytokines, A recently detected family of secondary and chemotactic cytokines, termed chemokines, now comprises 17 human members with leukocyte-selective chemotactic properties, Members of the so-called ''C-X-C'' chemokine subfamily, such as interleukin-8, Gro-alpha, and possibly the gamma-interferon-inducible protein IP-10, seem to be important for neutrophil- and/or T-lymphocyte-selective accumulation in inflamed skin because of their more neutrophil- or T-lymphocyte-, but not monocyte- or eosinophil-chemotactic properties. On the other hand, members of the ''C-C'' chemokine subfamily, such as monocyte chemotactic protein-1, RANTES, macrophage inflammatory protein-1 alpha, and MARC/monocyte chemotactic protein-3, attract monocytes, T-lymphocyte forms and subsets, eosinophils, and basophils, but not neutrophils, The cell-specific chemotactic properties as well as the release pattern, which seems to be at least in part tissue cell- and stimulus-specific, point to a possible role in chronic skin diseases, explaining parts of the disease-characteristic tissue infiltrates. The recent detection of novel chemokines with T-lymphocyte-type and subpopulation-specific chemotactic properties map facilitate understanding of disease-characteristic patterns of T-lymphocyte accumulation, including homing phenomena.