Dexamethasone inhibits tumor necrosis factor-α-induced cytokine secretion from spiral ligament fibrocytes

To investigate the effect of proinflammatory cytokines on spiral ligament (SL) fibrocytes and regulation of cytokines by dexamethasone (Dex), in vitro studies were performed in murine secondary cell cultures. Cultured SL fibrocytes were stimulated with tumor necrosis factor-alpha (TNF-alpha), and the secretion of various mediators was measured by enzynne-linked immunosorbent assay (ELISA) and reverse transcribed-polymerase chain reaction (RT-PCR). After stimulation with TNF-alpha, levels of keratinocyte-derived cytokine (KC), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) were elevated in the culture supernatant, and their corresponding messenger RNAs were detected in the cultured fibrocytes. When the cultures were incubated with both TNF-alpha and Dex, the levels of KC. MCP-1. MIP-2 and IL-6 were significantly lower than those in Cultures treated with TNF-alpha alone. The data suggest that Dex suppresses the inflammatory response in SL fibrocytes. Given that SL fibrocytes play a role in cochlear fluid and ion homeostasis, glucocrticoids may suppress the cochlear malfunction caused by SL inflammation. (c) 2004 Elsevier B.V. All rights reserved.