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 sub-population-specific chemotactic properties may facilitate understanding of disease-characteristic patterns of T-lymphocyte accumulation, including homing phenomena.