Human rTNF alpha augments anti-bacterial resistance in mice: potentiation of its effects by recombinant human rIL-1 alpha

Abstract

Treatment with human recombinant tumour necrosis factor-alpha (rTNF alpha) significantly enhanced resistance to Listeria monocytogenes infection in mice. The level of protection (which was dose-dependent and maximal at approximately 1.0 microgram per mouse) was similar to that previously reported for the monokine rIL-1 alpha, although somewhat greater amounts of rTNF alpha than rIL-1 alpha were required. Combined administration of suboptimal concentrations of rTNF alpha and rIL-1 alpha 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 rTNF alpha or IL-1 alpha that were themselves capable of inducing substantial protection. Combined administration of rTNF alpha and rIL-1 alpha 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 rTNF alpha and rIL-1 alpha was associated with a more rapid decline in serum colony-stimulating activity. Peritoneal macrophages from rTNF alpha- and rIL-1 alpha-treated listeria-infected mice did not demonstrate enhanced anti-listeria activity in vitro. These results provide further evidence for the potential benefits of rTNF alpha and other cytokines in promoting anti-bacterial resistance. They further suggest that use of combinations of cytokines is a strategy worthy of further consideration.