title: Modulation of Mycobacterium avium growth in vivo by cytokines: involvement of tumour necrosis factor in resistance to atypical mycobacteria.
abstract: 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 micrograms of interleukin-1 alpha and 1 micrograms 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.
authors.affiliation: Research Unit, Laval Hospital, Ste-Foy, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Denis
mesh_terms: D000818:Animals; D016207:Cytokines / Q000502:physiology*; D007106:Immune Sera; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009162:Mycobacterium avium / Q000254:growth & development / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D016207:Cytokines; D007106:Immune Sera; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma