Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice

• DOI: 10.1046/j.1365-2249.2002.01828.x
• Publication Date: 2003-03-11T10:31:51Z
• Authors: F ALVES-ROSA; M VULCANO; M BEIGIER-BOMPADRE; G FERNÁNDEZ; M PALERMO; M A ISTURIZ
• Keywords: Lipopolysaccharides; Mice, Inbred BALB C; Membrane Glycoproteins; Tumor Necrosis Factor-alpha; Toll-Like Receptors; Anti-Inflammatory Agents; Down-Regulation; Receptors, Cell Surface; Dexamethasone; Up-Regulation; 3. Good health; Toll-Like Receptor 4; Mice; 03 medical and health sciences; Receptors, Glucocorticoid; 0302 clinical medicine; Immune Tolerance; Animals; Drosophila Proteins; Gram-Negative Bacterial Infections; Interleukin-1

SUMMARY Endotoxin or lipopolysaccharide (LPS) tolerance may be partially due to the secretion of potent anti-inflammatory cytokines following severe Gram-negative infections, by low doses LPS. In this work, we describe effects interleukin-1β (IL-1β) and tumour necrosis factor alpha (TNF-α), two early secreted after LPS exposure, in induction tolerance. Our results demonstrate that mice treated with three daily 100 ng IL-1β were tolerant LPS-induced shock. However, TNF-α was unable induce an refractory state. Given fact increase plasma levels glucocorticoids, evaluated whether a injection dexamethasone (DEX) alone able reproduce LPS-like no signs refractoriness detected, except when DEX administered concomitantly dose does not corticosterone (12 ng/mouse). This found vitro up-regulation glucocorticoid receptors (GcR) peritoneal macrophages 24 h treatment. addition, is capable inducing down-regulation Toll-like receptor 4 (TLR4), crucial molecule signal transduction Taken together, our indicate can generate vivo, suggest regulation mechanisms TLR4, as well those involved expression GcR and/or would for these effects.