MODULATION OF MYCOBACTERIUM-AVIUM GROWTH-INVIVO BY CYTOKINES - INVOLVEMENT OF TUMOR-NECROSIS-FACTOR IN RESISTANCE TO ATYPICAL MYCOBACTERIA

The protective mechanisms associated with resistance to atypical mycobacteria infections are not clear. In an effort to broaden our understanding of the mechanisms involved, susceptible mice were infected with a virulent strain of M. avium and various treatments were applied so as to modify the course of the disease. Treatment with an antiserum against tumour necrosis factor-alpha (TNF-alpha) significantly enhanced the experimental infection, as judged by enumeration of colony-forming units (CFU) in the spleens and livers of infected mice, suggesting a role for TNF-alpha in resistance to M. avium. In other sets of experiments, recombinant cytokines were directly infused into infected mice. Infusion of recombinant interferon-gamma (IFN-gamma) did not modify the experimental infection significantly, and infusion of interleukin-2 was also without effect. Injection of TNF-alpha enhanced resistance in susceptible animals, as seen by a reduction in the viable bacilli recovered from the spleens and livers. In a final set of experiments, we demonstrate that combinations of cytokines may induce strong resistance against M. avium, namely injection of 1-mu-g of interleukin-1-alpha and 1-mu-g of TNF-alpha at 5-day intervals which was seen to eradicate M. avium in both spleens and livers of susceptible BALB/c mice. Overall, our results suggest that induction of protection against M. avium by treatment with cytokines may be feasible, and that TNF-alpha may be a pivotal molecule in resistance to M. avium.