Involvement of Cytokines in Determining Resistance and Acquired Immunity in Murine Tuberculosis

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Abstract
Herein we demonstrate that continuous infusion of either TNF-α or IFN-γ (104 U/day) via osmotic micropumps leads to an increased resistance of mice infected with a lethal dose (107) of M. tuberculosis H37Rv, associated with a decreased microbial growth in all target organs. This result was reinforced by the finding that infusion of antibodies against TNF-α or IFN-γ greatly enhanced susceptibility of naive mice to tuberculosis. In a final set of experiments, using neutralizing antibodies, we show that IFN-γ, not TNF-α is involved in determining acquired resistance against murine tuberculosis, as seen by the fact that acquired immunity is resistant to anti-TNF-α antibodies, yet sensitive to anti-IFN-γ antibodies. This suggests a role for both IFN-γ and TNF-α in determining innate resistance whereas IFN-γ may be the mediator of the anamnestic response.

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