Antibacterial resistance induced by recombinant interleukin 1 in myelosuppressed mice: effect of treatment schedule and correlation with colony-stimulating activity in the bloodstream.
We have investigated the effects of interleukin 1 (IL-1) administration on the ability of neutropenic mice to resist Pseudomonas aeruginosa challenge in vivo. Cyclophosphamide-treated mice received human rIL-1 beta at 7.0, 0.7, or 00.7 micrograms/kg, according to different regimens, to be challenged with a lethal ip inoculum of pseudomonas cells 5 days after myelosuppression. The repeated exposure of the neutropenic mice to an overall cytokine dosage of 7.0 or 0.7 micrograms/kg during the 4 days after myelosuppression was found to optimally restore the animals' antibacterial resistance. However, when administered as a single injection 24 hr before challenge, the same dosages of IL-1 had lower or no effect in enhancing survival, primarily leading only to a reduction in the amount of antipseudomonal chemotherapy required for cure. The regimen of IL-1 administration conferring optimal protection also resulted in a decrease in the number of pseudomonas cells recovered from the peritoneal cavity of infected mice. This regimen accelerated hematopoietic recovery in cyclophosphamide-treated mice. Assay of serum colony-stimulating activity (CSA) revealed that (a) cyclophosphamide treatment alone significantly increased the level of circulating CSA, (b) administration of a single dose of IL-1 to neutropenic mice induced an early, further increase in serum CSA, followed by depression, (c) a biphasic pattern of CSA response was also evident in mice repeatedly treated with IL-1. These results suggest that regulation of hematopoiesis may have an important role in the induction of antibacterial resistance in myelosuppressed hosts repeatedly treated with low dosages of IL-1.
Campanile
F
F
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Binaglia
L
L
Boraschi
D
D
Tagliabue
A
A
Fioretti
M C
MC
Puccetti
P
P
D000818:Animals; D001770:Blood Bactericidal Activity; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects; D007167:Immunotherapy; D007375:Interleukin-1 / Q000494:pharmacology / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D011552:Pseudomonas Infections / Q000628:therapy*; D011550:Pseudomonas aeruginosa; D011994:Recombinant Proteins; D013997:Time Factors
D005839:Gentamicins; D007375:Interleukin-1; D011994:Recombinant Proteins; D003520:Cyclophosphamide