EFFECT OF MURINE RECOMBINANT INTERFERON-GAMMA IN THE PROTECTION OF MICE AGAINST SALMONELLA

The ability of recombinant murine (rMu) interferon (IFN) -γ to activate anti-Salmonella-activity in normal mice and beige mutant (bg/bg) mice with Chediak-Higashi syndrome (CHS) was examined. Previous intraperitoneal (i.p.) injection of rMuIFN-γ (104 U per mouse) significantly hindered the bacterial growth in the peritoneal cavities, spleens and livers of the mice after the i.p. infection with Salmonella enteritidis No. 11 strain. It was also effective on the beige mice that have phagocytic cells with a genetically impaired bactericidal function, suggesting that IFN-γ activates the pathway irrelevant to the beige mutation. The effect was the maximum, when IFN-γ was given 6 h before the challenge. The effect seemed to be due to the augmentation of bactericidal capacity rather than the prevention of systemic spread of bacteria. Recombinant human IFN-αA/D (102-106 U per mouse), which produced effects identical to those of murine IFN-β, did not show such a bactericidal effect. Bactericidal activity enhancement was also seen in mice that had been injected with a small amount of rMuIFN-γ (102 U) and bacterial lipopolysaccharide (LPS) (10 ng) together at 6 h before the challenge, although the IFN-γ or LPS alone at these doses produced very little if any effect. Bactericidal effect enhancement was seen in mice that had been injected with IFN-γ at 6 h and LPS at 3 h before the challenge, while it could be hardly seen in mice injected with them in a reversed order. The simultaneous injections of rMuIFN-γ and LPS at 6 h in advance could confer a good protection against the infection with the S. tryphimurium LT2 strain. © 1989.