DIFFERENTIAL REGULATION OF INTERLEUKIN-4 AND INTERLEUKIN-13 PRODUCTION BY INTERFERON-ALPHA

Interferon alpha (IFN-alpha) has proven its clinical usefulness in a v ariety of diseases of diverse pathogenesis, In addition to direct anti viral effects, recent evidence suggests that its interaction with the cytokine cascade might contribute to its mechanism of action, This stu dy was undertaken to determine whether IFN-alpha influences the synthe sis of interleukin 4 (IL-4) and IL-13, two cytokines which share many biological properties on various cells and tissues and which have a pr ofound role in regulating immunological and inflammatory responses, Pe ripheral blood mononuclear cells (PBMC) from healthy volunteers were s timulated with Concanavalin A (ConA), phorbol myristate acetate (PMA), anti-CD3/CD28 mAbs, either alone or in various combinations, and incu bated with increasing concentrations of IFN-alpha, IL-4 and IL-13 mRNA was determined by Northern hybridizations and IL-4 and IL-13 protein synthesis was evaluated by specific enzyme-linked immunosorbent assay (ELISA), IFN-alpha led to a profound decrease of IL-13 mRNA expression after an incubation period of 5 h with ConA alone or in combination w ith PMA, whereas it showed no regulatory effect on IL-4 mRNA expressio n, After an incubation period of 24 h, the decrease in IL-13 mRNA expr ession after addition of IFN-alpha was even more pronounced, At the pr otein level, IFN-alpha increased IL-4 synthesis dose dependently regar dless of the mode of activation, This increase was most pronounced aft er stimulation with ConA or anti-CD28/PMA. In contrast, IL-13 synthesi s was strongly downregulated by IFN-alpha in a dose-dependent manner i rrespective of the activating agent, It is concluded that IL-4 and IL- 13, although showing similar biological effects, are differentially re gulated by IFN-alpha. (C) 1998 Academic Press Limited.