Premium
Hematologic Interactions of Endotoxin, Tumor Necrosis Factor Alpha (TNFα), Interleukin 1, and Adrenal Hormones and the Hematologic Effects of TNFα in Corynebacterium parvum ‐Primed Rats
Author(s) -
Ulich Thomas R.,
Castillo Juan,
Ni RongXiang,
Bikhazi Nadim
Publication year - 1989
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.45.6.546
Subject(s) - neutrophilia , monokine , tumor necrosis factor alpha , monocytosis , immunology , neutropenia , biology , medicine , endocrinology , cytokine , granulocytosis , interleukin , interleukin 6 , bone marrow , granulocyte , chemotherapy
Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL‐1) and causes peripheral lymphopenia and a dose response‐dependent initial neutropenia followed by a monophaslc neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL‐1 alone induces lymphopenia and a monophaslc neutrophilia. TNF‐plus‐IL‐1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS‐Induced lymphopenia. TNF‐plus‐IL‐1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS‐induced neutropenia is caused by TNF, while LPS‐induced neutrophilia is due to the combined effects of TNF and II‐1. TNF and IL‐1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram‐negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS‐induced lymphopenia, LPS‐induced neutropenia, and LPS‐induced neutrophilia. TNF‐plus‐LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF‐plus‐LPS‐treated rats and increased the neutrophilia. IL‐1 combined with LPS increased LPS‐induced neutrophilia, suggesting that endogenous IL‐1 also contributed to LPS‐induced neutrophilia. Corynebacterium parvum ‐primed rats with hyperplasia of the monocyte macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF‐induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL‐1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.