TY - JOUR
T1 - Synergy between tumor necrosis factor α and interleukin-1 in the induction of sickness behavior in mice
AU - Bluthé, R. M.
AU - Pawlowski, M.
AU - Suarez, S.
AU - Parnet, P.
AU - Pittman, Q.
AU - Kelley, K. W.
AU - Dantzer, R.
N1 - Funding Information:
recombinant human IL-1/3 and Dr. N.D. Staite (Upjohn, Kalamazoo, Michigan, U.S.A.) for providing recombinant human TNFa. Recombinant human IL-l receptor antagonist (IL-lra) was kindly provided by Dr. R. J. Vannice (Synergen, Boulder, Colorado, U.S.A.). We would like to thank Viviane Tridon for surgery, Ghislain Boulon for training mice, and Dr. S. Kent for critical reading of the manuscript. This work was supported by INSERM and INRA. Dr. Quentin Pittman was supported by INSERM, INRA, and the Alberta Heritage Foundation for Medical Research.
PY - 1994
Y1 - 1994
N2 - Like interleukin-1, recombinant human tumor necrosis factor α (TNFα) has been found to decrease social exploration and induce weight loss in mice in a dose and time-dependent manner. The present study was carried out to study the interaction between these two cytokines. Mice were injected IP with subthreshold doses of TNFα (2.5 μg/mouse) and IL-1β (50 ng/mouse). Social exploration was decreased 2 and 4 h after injection of TNF and IL-1, but body weight was not affected. Subthreshold doses of TNFα (90 ng/mouse) and IL-1β (100 pg/mouse) were also injected intracerebroventricularly (ICV). Social exploration was decreased 1.5 and 3 h after injections of the two cytokines and body weight was decreased for 6 h. To test the possibility of central induction of IL-1 by TNFα, mice pretreated with IL-1 receptor antagonist (IL-1ra, 1.8 μg/mouse, ICV) were injected with 90 ng TNFα. Pretreatment with IL-1ra antagonized the depressive effect of TNFα on behavior, but had no effect on weight loss induced by this cytokine. These results suggest that TNFα-induced behavioral alterations are mediated by endogenously released IL-1, whereas metabolic changes are dependent on the release of other cytokines.
AB - Like interleukin-1, recombinant human tumor necrosis factor α (TNFα) has been found to decrease social exploration and induce weight loss in mice in a dose and time-dependent manner. The present study was carried out to study the interaction between these two cytokines. Mice were injected IP with subthreshold doses of TNFα (2.5 μg/mouse) and IL-1β (50 ng/mouse). Social exploration was decreased 2 and 4 h after injection of TNF and IL-1, but body weight was not affected. Subthreshold doses of TNFα (90 ng/mouse) and IL-1β (100 pg/mouse) were also injected intracerebroventricularly (ICV). Social exploration was decreased 1.5 and 3 h after injections of the two cytokines and body weight was decreased for 6 h. To test the possibility of central induction of IL-1 by TNFα, mice pretreated with IL-1 receptor antagonist (IL-1ra, 1.8 μg/mouse, ICV) were injected with 90 ng TNFα. Pretreatment with IL-1ra antagonized the depressive effect of TNFα on behavior, but had no effect on weight loss induced by this cytokine. These results suggest that TNFα-induced behavioral alterations are mediated by endogenously released IL-1, whereas metabolic changes are dependent on the release of other cytokines.
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U2 - 10.1016/0306-4530(94)90009-4
DO - 10.1016/0306-4530(94)90009-4
M3 - Article
C2 - 8190839
AN - SCOPUS:0028279551
SN - 0306-4530
VL - 19
SP - 197
EP - 207
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 2
ER -