Comparison of the effects of IL-1 alpha and TNF-alpha on phagocyte accumulation and murine antibacterial immunity.
IL-1 and TNF both are reported to increase host antibacterial resistance. To directly compare their effects on tissue phagocyte accumulation and antibacterial activity, we infused recombinant human IL-1 alpha and TNF-alpha into C3H/HeJ mice. Although IL-1, at a dose of 1 microgram/day, did not significantly elevate blood neutrophil concentrations, it increased the number of PMNs within the spleen three to fourfold within 2 days. Similar neutrophil accumulation also occurred in the lungs, bone marrow, and liver of treated animals without detectable changes in macrophage numbers. IL-1 also increased myelopoiesis in the spleen by Days 3-4 of infusions. The capacity of splenocytes from IL-1-treated animals to kill Listeria monocytogenes in vitro and to suppress listeria proliferation in vivo after the intravenous infusion of bacteria both rose in parallel with PMN accumulation. Comparable doses of TNF also enhanced listeria killing in vivo but in contrast to IL-1, it significantly depressed peripheral blood neutrophil counts, and inhibited splenic neutrophil accumulation and in vitro listericidal activity in listeria-infected mice. Our results suggest that IL-1 enhances host resistance to infection by increasing tissue neutrophil accumulation while TNF protects by a different mechanism, despite a net inhibitory effect on neutrophil accumulation.
Kurlander
R J
RJ
Department of Medicine, Duke Medical Center, Durham, North Carolina 27710.
Hoffman
M
M
Kratz
S S
SS
Gates
J
J
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha