Immunotoxicity of in vitro vanadium exposures: effects on interleukin-1, tumor necrosis factor-alpha, and prostaglandin E2 production by WEHI-3 macrophages.

Treatment of cultured mouse macrophages with either of two different vanadium compounds was shown to affect the production/release of two major immunoregulatory cytokines. The pentavalent vanadium compound ammonium metavanadate was shown previously to disrupt cell-mediated immunity at the earliest stages of an in vivo anti-Listerial response, in that mice treated with vanadium displayed decreased accessory cell recruitment and numbers of activated macrophages at infection sites. To determine whether these effects were due to vanadium-induced alterations in the production of biologically-active mediators, mouse macrophage-like WEHI-3 cells were treated in vitro with ammonium metavanadate or vanadium pentoxide prior to stimulation with lipopolysaccharide endotoxin (LPS). After stimulation, monokine (tumor necrosis factor-alpha and interleukin-1) and prostaglandin E2 (PGE2) activities were assessed. Both vanadium compounds decreased recovered monokine activities; measured TNF alpha concentrations were also reduced. Spontaneous release of the IL-1/TNF-regulating prostanoid PGE2 was significantly increased by the highest concentration of vanadate tested, although LPS-stimulated PGE2 production was unaffected by either compound. These results indicate that, in vitro, pentavalent vanadium can interfere with immunoregulatory mediators critical for maintaining host immunocompetence.