INTERLEUKIN-1 IS INVOLVED IN MOUSE RESISTANCE TO MYCOBACTERIUM-AVIUM

In this study, we examined the contribution of the monokine interleuki n-1 (IL-1) in mouse resistance to the intracellular pathogen Mycobacte rium avium. The effect of neutralizing endogenous IL-1 in mouse macrop hage resistance to M. avium infection was investigated. Infection of m ouse 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-I receptor antagonist (IL-1ra) at doses of 5 mu g daily , which neutralized endogenous IL-1, failed to significantly modify th e intracellular growth of M. avium. Mice were injected with M. avium B 101 by the intravenous route, and the growth of the mycobacteria was m onitored in the organs of intact mice and in those of mice that receiv ed 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 spl eens. Repeated injections of IL-1ra into M. avium-infected mice result ed in moderately enhanced growth of the bacilli in the livers and sple ens but in much enhanced grow th 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. The se data argue for a role for IL-1 in host resistance to M. avium infec tions.