Involvement of Interleukin-6 and Interferon-α in the Poly(A).Poly(U)-Induced 2',5'-Ohgoadenylate Synthetase Activity in the Mouse Monocyte-Macrophage Cell Line,J774A 1

The synthetic polyribonucleotide poly(A).poly(U) induces 2',5'-oligoadenylate synthetase activity in the murine macrophage cell line J774A₁. The possible role of several cytokines involved in macrophage activation (i.e., IL-1, IL-6, TNF, and IFN) was examined in the present study. It was first demonstrated that among the anticytokine antibodies, only monoclonal antibodies directed against IL-6 inhibited the induction 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 J774A₁ cells in a time- and dose-dependent manner. Consequently, the effect of IL-6 on 2',5'-oligoadenylate synthetase activity was studied. IL-6 either alone or in combination with IL-1 and TNF did not induce 2',5'-oligoadenylate synthetase activity. IL-6 did not potentiate IFN-γ-induced 2'-5'-oligoadenylate synthetase activity. In contrast, addition of IL-6 to the incubation medium potentiated the stimulation of 2'5'-oligoadenylate synthetase activity by IFN-α. These results suggest that IL-6 is a necessary but not sufficient factor in the induction of 2'-5'-oligoadenylate synthetase activity in the J774A₁ cell line by poly(A) . poly(U).