Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor

Abstract

Cultured normal human fibroblasts were stimulated to produce neutrophil-activating protein/interleukin-8 (IL-8) in response to IL-1 alpha (0.1-1000 U/ml) or tumour necrosis factor (TNF) alpha (0.1-1000 U/ml). Induction of mRNA for IL-8 in fibroblasts was rapid (within 30 min) and maximal responses were obtained with either 100 U/ml IL-1 alpha or 100 U/ml TNF alpha. Expression of mRNA for IL-8 was accompanied by the production of high levels of neutrophil chemotactic activity. IL-1 alpha (1000 U/ml), but not TNF alpha, induced mRNA for IL-8 in cultured normal human keratinocytes. The relevance of production of IL-8 by these cell types was evaluated further by comparing the local inflammatory effects of IL-1 alpha, TNF alpha and IL-8. Intradermal injection of either recombinant IL-8, IL-1 alpha or TNF alpha lead to a similar in vivo effect, i.e. dose-dependent accumulation of lymphocytes and polymorphonuclear leucocytes at sites of injection. The in vivo attraction of neutrophils and lymphocytes to the site of injection by TNF or IL-1 (which is not chemotactic for neutrophils or lymphocytes in vitro), may be partly mediated by locally produced IL-8. Thus, IL-8 may be a vital participant in the cascade of interacting cytokines that is induced by tissue injury and immunologically induced inflammation.