INVOLVEMENT OF INTERLEUKIN-6 AND INTERFERON-ALPHA IN THE POLY(A)CENTER-DOT-POLY(U)-INDUCED 2',5'-OLIGOADENYLATE SYNTHETASE-ACTIVITY IN THE MOUSE MONOCYTE-MACROPHAGE CELL-LINE, J774A

The synthetic polyribonucleotide poly(A) . poly(U) induces 2',5'-oligo adenylate synthetase activity in the murine macrophage cell line J774A (1). The possible role of several cytokines involved in macrophage act ivation (i.e., IL-1, IL-6, TNF, and IFN) was examined in the present s tudy. It was first demonstrated that among the anticytokine antibodies , only monoclonal antibodies directed against IL-6 inhibited the induc tion of 2',5'-oligoadenylate synthetase by poly(A) . poly(U) in a dose -dependent manner. Moreover, it was established that poly(A) . poly(U) elicited IL-6 production in J774A(1) cells in a time- and dose-depend ent manner. Consequently, the effect of IL-6 on 2',5'-oligoadenylate s ynthetase activity was studied. IL-6 either alone or in combination wi th IL-1 and TNF did not induce 2',5'-oligoadenylate synthetase activit y. IL-6 did not potentiate IFN-gamma-induced 2'-5'-oligoadenylate synt hetase activity. In contrast, addition of IL-6 to the incubation mediu m potentiated the stimulation of 2'-5'-oligoadenylate synthetase activ ity by IFN-alpha. These results suggest that IL-6 is a necessary but n ot sufficient factor in the induction of 2'-5'-oligoadenylate syntheta se activity in the J774A(1) cell line by poly(A) . poly(U).