Enhancement of antibacterial resistance of neutropenic, bone marrow-suppressed mice by interleukin-1 alpha.
The effect of recombinant human interleukin-1 alpha (IL-1) on the resistance of normal and bone marrow-suppressed mice against bacterial infection was evaluated. IL-1 induced neutrophilia and enhanced the resistance of normal mice against acute, systemic intraperitoneal infection with Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus. Mice with cyclophosphamide-induced bone marrow suppression were neutropenic and exhibited increased susceptibility to infection. Treatment of neutropenic C57BL/6 and C3H/HeJ mice with IL-1 before infection accelerated recovery of peripheral neutrophil counts and stimulated resistance against infection. Increases in neutrophils and enhancement of resistance induced by IL-1 were both dose and time dependent. Both neutrophilia and augmented resistance to infection were eliminated by a second dose of cyclophosphamide administered during the IL-1 treatments. Bone marrow-suppressed mice treated with IL-1 showed, at 4 h postinfection, greater increases in peripheral blood neutrophils and in numbers of peritoneal exudate neutrophils than suppressed mice treated with vehicle. The data suggest that the IL-1-stimulated recovery of myelopoiesis is an important factor in the enhancement of antibacterial resistance in bone marrow-suppressed, neutropenic mice. These findings indicate that IL-1 may be efficacious in limiting the duration of the neutropenia and of the increased risk for the development of bacterial infection associated with bone marrow suppression.
Department of Immunopharmacology, Hoffmann-LaRoche, Inc., Nutley, New Jersey 07110.
K W
KW
McIntyre
J
J
Unowsky
W
W
DeLorenzo
W
W
Benjamin
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000380:Agranulocytosis / Q000276:immunology*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D007113:Immunity, Innate / Q000187:drug effects; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000008:administration & dosage / Q000627:therapeutic use*; D007700:Kinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009503:Neutropenia / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D003520:Cyclophosphamide; D005472:Fluorouracil