ARS | Publication request: CORTICOID AND ANTI-CORTICOID CONTROL OF TUMOR NECROSIS FACTOR ALPHA SECRETION BY PORCINE MACROPHAGES

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: November 12, 1997
Publication Date: N/A

Technical Abstract: The ability of glucocorticoids and antiglucocorticoids to control production of immunopeptides in pigs is of economic and biologic relevance. The effect of a synthetic glucocorticoid (dexamethasone, DEX) and an antiglucocorticoid (RU486) on porcine macrophage production of tumor necrosis factor alpha (TNF) was studied. Peripheral blood macrophages obtained by density gradient centrifugation were cultured (37 C, 5% CO2) i RPMI + 10% heat-inactivated fetal bovine serum (HIFBS) containing 20 ng/ml recombinant human colony-stimulating factor-1 (CSF-1) with medium changes at 3-day intervals. Medium was aspirated and cultures were re-supplied with RPMI + 1% HI-horse serum containing lipopolysaccharide (LPS; 0 to 100 ng/ml), DEX (10**-6 to 10**-10 M) and/or RU486 (10**-6 M). Medium concentration of TNF was determined by a specific ELISA. LPS induced a dose- and time-dependent increase in TNF. DEX dose-dependently inhibited LPS-induced TNF production (maximum effect at 10**-8 M). RU486 dose dependently attenuated the ability of DEX to inhibit LPS-induced TNF production. In time course experiments, pre-treatment (-6 h) with DEX (10**-6 M) did not affect the initial (3 h) increase in TNF production, but abolished subsequent LPS-induced increases in TNF (up to 24 h). Addition of DEX (10**-6 M) after LPS addition (+6 h) inhibited further TNF production. Glucocorticoids suppress production of TNF in a receptor mediated fashion, but may not entirely prevent the LPS-induced activation of pig macrophages in vitro. Increased comprehension of the dynamic intercommunication of the endocrine and immune systems will enhance strategic development of animal models of sepsis.