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.
Department of Environmental Medicine, New York University Medical Center, Tuxedo 10987.
M D
MD
Cohen
E
E
Parsons
R B
RB
Schlesinger
J T
JT
Zelikoff
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014639:Vanadium / Q000633:toxicity*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014639:Vanadium; D015232:Dinoprostone