Separate and combined effects of recombinant interleukin-1 alpha and gamma interferon on antibacterial resistance.
Our laboratory has previously reported that administration of murine recombinant interleukin 1 alpha (rIL-1 alpha) substantially enhanced the resistance of mice to Listeria monocytogenes infection. Other investigators have reported that gamma interferon (IFN-gamma) plays a pivotal role in antilisteria resistance. In the present study, we have defined doses of human rIL-1 alpha that enhanced the antilisteria resistance of mice. We then addressed the possibility that combined immunotherapy with rIL-1 alpha and recombinant IFN-gamma (rIFN-gamma) might result in an additive or synergistic enhancement of antibacterial resistance. Simultaneous administration of rIL-1 alpha and rIFN-gamma enhanced antilisteria resistance (at 3 days after infection) to a greater extent than did either cytokine alone, although the results did not imply a synergistic action between the two cytokines. Experiments which examined the effects of the timing of cytokine administration indicated that maximal protection was observed when rIL-1 alpha and rIFN-gamma were administered together concomitantly with the L. monocytogenes challenge. When we compared the separate and combined protective effects of rIL-1 alpha and rIFN-gamma throughout the course of a primary L. monocytogenes infection, we observed an additive effect of the two cytokines only at 3 days after challenge, the time at which the peak bacterial burden occurs in the spleens and livers of infected mice. Histopathological comparisons of livers and spleens from cytokine-treated and control listeria-infected mice verified that cytokine treatment reduced the severity of tissue damage in cytokine-treated listeria-infected mice. In an attempt to provide a potential mechanism for the protective effects of rIL-1 alpha and rIFN-gamma administration, we compared levels of colony-stimulating activity in sera from cytokine-treated and control listeria-infected mice. The highest levels of colony-stimulating activity were detected in sera from control listeria-infected mice; somewhat lower levels were found in sera from listeria-infected mice that received rIL-1 alpha and rIFN-gamma either alone or in combination.
Kurtz
R S
RS
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706.
Young
K M
KM
Czuprynski
C J
CJ
D000818:Animals; D003115:Colony-Stimulating Factors / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007371:Interferon-gamma / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000008:administration & dosage*; D008088:Listeriosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D011994:Recombinant Proteins
D003115:Colony-Stimulating Factors; D007375:Interleukin-1; D011994:Recombinant Proteins; D007371:Interferon-gamma