In vivo modulation of atypical mycobacterial infection: adjuvant therapy increases resistance to Mycobacterium avium by enhancing macrophage effector functions.

Susceptible BALB/c mice were infected iv with a strain of Mycobacterium avium and infused with different biological response modifiers (BRM) in a gel delivery system so as to modify the progression of the infection in a beneficial fashion. Infusion of IL-2 or IL-4 in hydrophobic gels led to no significant enhancement of resistance. Infusion of muramyl dipeptide in hypromellose led to a significant enhancement of resistance against the M. avium, as seen by a significant reduction of colony-forming units (CFU) in the spleens of infected mice. Similarly, infusion of interleukin-1 beta in hypromellose in infected mice led to a significant reduction in CFU counts in the organs of mice. The mechanism(s) responsible for this enhanced resistance was studied further. It was found that infected mice developed profound immunosuppression, as judged by mitogenic and antigenic stimulation. Mice infused with MDP/hypromellose developed a similar immuno-suppression, suggesting that this adjuvant immunotherapy did not act by stimulating a T-cell response or by abrogating a putative suppressive phenomenon. Macrophages from mice infused with MDP alone were no more bacteriostatic for a virulent M. avium than control cells. However, macrophages from infected mice infused with MDP/hypromellose were more bacteriostatic for M. avium than cells from mice infected with M. avium and infused with the hydrophobic gel only. Overall, these results suggest that adjuvant immunotherapy is beneficial in M. avium infections.