Defective production of interleukin 6 by macrophages from C3H/HeJ mice: differential stimulation of interleukin 1 and interleukin 6 induction

Resident macrophages from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, in contrast with macrophages from other mouse strains, produced neither interleukin 6 (IL-6) nor interleukin 1 (IL-1) spontaneously. The stimulation of C3H/HeJ macrophages with poly(I:C), LPS or, to a lesser extent, muramyl dipeptide (MDP), induced the production of both cytokines. High levels of intracellular IL-1 activity were produced which were not released in surrounding media unless silica was added to stimulated cells. On the other hand, IL-6 was secreted in the absence of any additional stimulus, hence also in the absence of extracellular IL-1. The kinetics of IL-1 and IL-6 production by LPS-stimulated macrophages were studied. Intracellular IL-1 produced by stimulated C3H/HeJ macrophages reached the levels produced by macrophages from C3H/HeN mice. IL-6-induced secretion, however, was about 5-fold less important than in C3H/HeN macrophages, suggesting a quantitative defect rather than an intrinsic defect in IL-6 production. © 1991.