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Prevention of Fatal Infections by Recombinant Human Interleukin 1 in Normal and Anticancer Drug-treated Mice

First Department of Internal Medicine [T. M., Y. M., S. Y.] and Department of Microbiology and Immunology [K. S.], Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-01, Japan

The preventive capability of interleukin 1 (IL-1) against bacterial infections was estimated in normal and anticancer drug-treated BALB/c mice in comparison with OK432, granulocyte colony-stimulating factor, interferons and , and interleukin 2. Pretreatment with IL-1 (days -4 and -2) resulted in a significantly higher survival rate in normal mice inoculated i.p. with Klebsiella pneumoniae, Pseudomonas aeruginosa or Listeria monocytogenes (day 0). The i.p. and s.c. administrations of IL-1 were equally effective for the induction of antibacterial resistance. Pretreatment with OK432 showed an equal degree of resistance to i.p. infection but was effective only by i.p. administration. Enhanced antibacterial resistance by IL-1 and OK432 was also observed in cyclophosphamide- and aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated (day -5) normal hosts and in cyclophosphamidetreated tumor-bearing hosts. In the case of granulocyte colony-stimulating factor (i.p. or s.c.) (days -4 to -1), a statistical difference in survival rate between granulocyte colony-stimulating factor and its vehicle-treated groups was observed in cyclophosphamide-pretreated hosts, but not in normal hosts or aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated hosts. Viable bacteria in the peritoneal cavity and blood at 12 h after i.p. infection of K. pneumoniae correlated well with the survival rate. In IL-1-pretreated hosts, the earlier and increased accumulation of neutrophils into peritoneal cavity after the infection was observed and the number of inflammatory cells in peritoneal cavity correlated well with the survival rate. The enhanced resistance to bacterial infection by IL-1 was suggested to be in part due to the enhanced cellular defense mechanisms. The prophylactic administration of IL-1 would be beneficial for the management of serious infections in cancer patients.

¹ To whom requests for reprints should be addressed.

Received 5/15/89. Revised 12/11/89.

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