Recombinant murine interleukin-1 alpha enhancement of nonspecific antibacterial resistance.
In this study we report that treatment with recombinant murine interleukin-1 alpha (rIL-1 alpha) significantly enhanced the resistance of mice to infection by the facultative intracellular pathogen Listeria monocytogenes. The greatest level of protection was observed at a dose of 1,000 lymphocyte-activating factor units (approximately 0.17 micrograms) of rIL-1 alpha per mouse. Although rIL-1 alpha enhanced antibacterial resistance when administered either intravenously or intraperitoneally, greater protection was observed when the rIL-1 alpha and the L. monocytogenes challenge were given by the same parenteral route. When the intravenous route was used, antibacterial resistance was maximal when the rIL-1 alpha and L. monocytogenes were injected concomitantly. In contrast, intraperitoneal administration of rIL-1 alpha was most effective when given 48 h before an intraperitoneal L. monocytogenes challenge. Based on the following lines of evidence, we concluded that contaminating lipopolysaccharide (LPS) was unlikely to be responsible for the enhanced antibacterial resistance that was observed: (i) LPS was not detectable (less than 0.2 ng/ml by the lysate assay) at the concentration of rIL-1 alpha that was injected; (ii) polymyxin B did not abrogate rIL-1 alpha-enhanced antibacterial resistance; (iii) rIL-1 alpha treatment enhanced the antibacterial resistance of LPS-nonresponsive C3H/HeJ mice; and (iv) injection of up to 10 micrograms of LPS per mouse (calculated to be greater than 50,000 times the concentration of LPS in the rIL-1 alpha administered) failed to duplicate the marked enhancement of antibacterial resistance that was mediated by rIL-1 alpha. These data provide evidence for the beneficial role of IL-1 in nonspecific antibacterial resistance.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007113:Immunity, Innate / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008088:Listeriosis / Q000276:immunology*; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins