Protective effect of recombinant tumor necrosis factor-α in murine salmonellosis

The enhancement of resistance by i.p. administration of murine rTNF-α into mice against i.p. challenge with virulent Salmonella typhimurium was studied. Administration of TNF-α (5x 10⁴ U/mouse) into mice at 6 or 12 h before the challenge with S. typhimurium organisms enhanced the bactericidal capacity in the peritoneal cavities of the mice. The diminution of the infecting organism in the peritoneal cavities of the TNF-α-treated mice was not due to the systemic spread of the organism inasmuch as few organisms were recovered from other areas such as the spleen and liver. The TNF-α treatment effected a slight increase of neutrophils in the peritoneal cavity, but did not effect an increase of macrophages, including Ia-bearing macrophages. The survival rate of mice infected with Salmonella was improved by the i.p. injection of TNF-α before infection. Co-administration of smaller doses of TNF-α (5 x 10³ U) and murine rIFN-γ (10² U) at 6 h before the challenge also effectively enhanced bactericidal activity and protectivity. The cooperative effect of TNF-α and IFN-α was only seen when these recombinant cytokines were injected together at the proper time before the challenge. Injection of rabbit anti-TNF-α serum abolished the effects of TNF-α and the cooperative effect of TNF-α and IFN-γ. Furthermore, the serum could abolish the cooperative effect of IFN-γ and LPS on bactericidal activity, suggesting participation of LPS-induced TNF-α in the cooperation.