RECOMBINANT HUMAN ALPHA LYMPHOTOXIN (TUMOR NECROSIS FACTOR-BETA) INDUCES PERIPHERAL NEUTROPHILIA AND LYMPHOPENIA IN THE RAT

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  • 1 July 1987
    • journal article
    • research article
    • Vol. 128  (1) , 5-12
Abstract
Recombinant human alpha lymphotoxin (rLT) administered intravenously to Lewis rats induces peripheral neurtrophilia and lymphopenia in a dose-response dependent fashion. A dose of 30,000 units of rLT induced a neutrophilia (1589 .+-. 326 to 5554 .+-. 1050 neutrophils/cu mmm) and lymphopenia (10,368 .+-. 992 to 4636 .+-. 878 lymphocytes/cu mm) at 2 hours after injection that was highly significant (P < 0.001 and P < 0.001, respectively) in comparison with vehicle controls. The kinetics of the neutrophilia that peaked at 2 hours as well as of the lymphopenia were highly reminiscent of the neutrophilia and lymphopenia following intravenous administration of either recombinant human interleukin-1 (IL-1) .alpha. or .beta. to rats. The peripheral neutrophilia was accompanied by a significant depletion of bone marrow neutrophils (P < 0.001), as is also known to occur after administration of IL-1. Systemic blood pressure was not affected by rLT, which suggested that the changes in circulating leukocytes subsets were not attributable to hemodynamic changes nor to the hemodynamic-change-related release of adrenal hormones. Adrenalectomy did not alter the rLT-induced neutrophilia or lymphopenia, which suggested that rLT does not mediate its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones. Preteatment of rats with dexamethasone, indomethacin, or aspirin also did not alter rLT-induced neutrophilia or lymphopenia, which suggested that rLT-induced hematologic effects were not mediated via arachidonic acid metabolites, in stark contrast to IL-1 induced neutrophilia, which is inhibited by both dexamethasone and indomethacin.