Heat shock prevents lipopolysaccharide-induced tumor necrosis factor-alpha synthesis by rat mononuclear phagocytes.
Tumor necrosis factor-alpha (TNF-alpha), a mononuclear phagocyte-derived peptide is known to participate in the pathogenesis of fever. To determine whether a feedback mechanism exists by which elevated temperatures influence TNF-alpha generation, we have examined the effects of heat shock on the in vitro synthesis of TNF-alpha by rat glomeruli, inflammatory peritoneal macrophages and blood monocytes. Preexposure of peritoneal macrophages to elevated temperatures for 20 min decreased the subsequent lipopolysaccharide-induced release of TNF-alpha bioactivity. The mean reductions were 11.9 +/- 5.0%, 86.3 +/- 12.0%, and 95.2 +/- 3.5% after pretreatment at 39, 41 and 43 degrees C, respectively. Reductions, that were transient, were maximum when lipopolysaccharide was added 0-2 h after heat shock. They correlated with the decreased release of immunoreactive TNF-alpha and the decreased expression of both cell-associated TNF-alpha molecule and TNF-alpha mRNA. Heat shock-induced inhibition of TNF-alpha release was independent of variations of prostaglandin synthesis, but was possibly related to the induction of heat-shock proteins since (a) macrophages exposed to heat shock synthesized the major 70- and 90-kDa heat-shock proteins, and (b) chemical inducers of the heat-shock response were also effective inhibitors of TNF-alpha release. The mean reduction of TNF-alpha release after pretreatment at 41 degrees C was found to be identical in glomerular tissue (82.0 +/- 7.5%), but significantly less in blood monocytes (43.9 +/- 10.9%). This supports the hypothesis that a negative-feedback mechanism exists between elevated temperature and lipopolysaccharide-induced TNF-alpha synthesis, and suggests that this regulation is less active in blood monocytes than in tissue macrophages.
Fouqueray
B
B
INSERM U. 64, Hôpital Tenon, Paris, France.
Philippe
C
C
Amrani
A
A
Perez
J
J
Baud
L
L
D000818:Animals; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha