Interleukin-1 is involved in mouse resistance to Mycobacterium avium

In this study, we examined the contribution of the monokine interleukin-1 (IL-1) in mouse resistance to the intracellular pathogen Mycobacterium avium. The effect of neutralizing endogenous IL-1 in mouse macrophage resistance to M. avium infection was investigated. Infection of mouse peritoneal macrophages with M. avium B101 was shown to result in significant IL-1 beta release by cells at 4 and 7 days postinfection. Addition of IL-1 receptor antagonist (IL-1ra) at doses of 5 micrograms daily, which neutralized endogenous IL-1, failed to significantly modify the intracellular growth of M. avium. Mice were injected with M. avium B101 by the intravenous route, and the growth of the mycobacteria was monitored in the organs of intact mice and in those of mice that received repeated high doses of IL-1ra. The infection with M. avium elicited the production of large amounts of IL-1 in the lungs, livers, and spleens. Repeated injections of IL-1ra into M. avium-infected mice resulted in moderately enhanced growth of the bacilli in the livers and spleens but in much enhanced growth in the lungs. The enhanced growth of M. avium in the lungs correlated with a diminished inflammatory influx of cells (particularly neutrophils) in the bronchoalveolar space. These data argue for a role for IL-1 in host resistance to M. avium infections.