An anti-tumor necrosis factor antibody suppresses sleep in rats and rabbits

It is hypothesized that tumor necrosis factor (TNF) is an endogenous sleep-promoting substance. In the present experiments we studied the effects of a monoclonal anti-TNF antibody in rats and rabbits. Seven rats and 14 rabbits were implanted with electroencephalographic electrodes, a brain thermistor and an intracerebroventricular guide cannula. The animals were injected with saline, control IgG, and monoclonal hamster anti-murine-TNF antibodies (TNFab) on 3 separate days. Ten micrograms TNFab suppressed non-rapid-eye-movement sleep (NREMS) in rats. In rabbits, 2.5 micrograms TNFab did not affect sleep but decreased brain temperature; in contrast, 25 micrograms TNFab suppressed NREMS without affecting brain temperature. These results are consistent with the hypothesis that endogenous TNF plays an important role in sleep regulation.