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.