Antiserum against tumor necrosis factor increases stress hyperthermia in rats.
Psychological stress (e.g., exposure to a novel environment) causes a rapid rise in body temperature in rats. In this study, we examined the roles of physical activity and the immune cytokine tumor necrosis factor or cachectin (TNF) in this temperature change. The elevation in temperature of rats exposed to cage-switch stress during the day correlated poorly with the increase in activity (r = 0.07; P = 0.84) and, during cage switch at night, correlated negatively (r = 0.64; P = 0.04). TNF was not detected in the plasma or cerebrospinal fluid of rats after exposure to open-field stress. However, the injection of antiserum against TNF 3.5 h before exposure to the stress of being in an open field resulted in a significantly greater hyperthermia than was seen in the control serum-injected rats (1.38 +/- 0.11 vs. 0.79 +/- 0.14 degrees C; P = 0.002). The peak temperature change after cage-switch stress was similarly increased in rats that had been injected with anti-TNF (0.82 +/- 0.08 vs. 0.50 +/- 0.08 degrees C; P = 0.016). This enhanced hyperthermia is similar to the excessively high fever that occurs during the later phase of lipopolysaccharide fever in animals that have been injected with antiserum against TNF. These data support the hypotheses that stress hyperthermia is a true fever and that TNF is an endogenous antipyretic, limiting the magnitude of this fever.
Long
N C
NC
Departments of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Vander
A J
AJ
Kunkel
S L
SL
Kluger
M J
MJ
D000818:Animals; D001831:Body Temperature; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D007106:Immune Sera; D008070:Lipopolysaccharides; D008297:Male; D009043:Motor Activity / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000150:complications*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D007106:Immune Sera; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha