HYPOTHERMIA AND HYPOGLYCEMIA INDUCED BY ANTI-CD3 MONOCLONAL-ANTIBODY IN MICE - ROLE OF TUMOR-NECROSIS-FACTOR

The possible involvement of tumor necrosis factor‐α (TNF) in the metabolic disturbances induced by anti‐CD3 monoclonal antibodies (mAb) was analyzed in DBA/2 mice injected with 50 μg of the anti‐murine CD3 mAb 145‐2C11. First, we found that 145‐2C11 induces a profound hypothermia maximal between 3 h and 6 h after the injection (at 3 h: − 3.0 ± 0.1 °C) as well as hypoglycemia (blood glucose levels at 6 h and 24 h: 76 ± 13 mg/100 ml and 92 ± 22 mg/100 ml, respectively, p < 0.001 as compared with control values). These metabolic changes are preceded by the release of TNF into the circulation (peak serum TNF levels at 2 h: 50 ± 23 pg/ml, p < 0.01 as compared with controls). The release of TNF induced by 145‐2C11 depends on the effect of the mAb on T cells as it is not observed in athymic nude mice while lipopolysaccharide‐resistant C3H/HeJ mice also display a significant rise in serum TNF (peak levels at 2 h: 59 ± 44 pg/ml). Pretreatment of DBA/2 mice with 12 mg of rabbit anti‐murine TNF antibodies completely prevents the hypothermia while the hypoglycemia is significantly attenuated. Finally, F(ab')2 fragments of 145‐2C11 induce only a transient hypoglycemia (blood glucose levels at 6 h: 109 ± 14, p < 0.001 as compared with controls) but neither hypothermia nor significant TNF release. We conclude that TNF is a major mediator of the acute metabolic changes induced by the intact form of 145‐2C11. Copyright © 1990 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim