Human rTNFα augments anti-bacterial resistance in mice: potentiation of its effects by recombinant human rIL-1α.

Treatment with human recombinant turnout necrosis factor-α (rTNFα) significantly enhanced resistance to Listeria monocytogenes infection in mice. The level of protection (which was dose-dependent and maximal at approximately 1·0 μg per mouse) was similar to that previously reported for the monokine rIL-1α, although somewhat greater amounts of rTNFα than rIL-1α were required. Combined administration of suboptimal concentrations of rTNFα and rIL-1α resulted in significant enhancement of resistance beyond that obtained with either monokine alone, whereas further increases in anti-listeria resistance were not observed at doses of rTNFα or IL-1α that were themselves capable of inducing substantial protection. Combined administration of rTNFα and rIL-1α was associated with a delay in onset and lessening in severity of the lymphopenia that accompanied L. monocytogenes infection. The reduced bacterial burden in the spleens and livers of mice treated with rTNFα and rIL-1α was associated with a more rapid decline in serum colony-stimulating activity. Peritoneal macrophages from rTNFα- and rIL-1α-treated listeria-infected mice did not demonstrate enhanced anti-listeria activity in vitro. These results provide further evidence for the potential benefits of rTNFα and other cytokines in promoting anti-bacterial resistance. They further suggest that use of combinations of cytokines is a strategy worthy of further consideration. [ABSTRACT FROM AUTHOR]