SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR (P75) DOES NOT ATTENUATE THE SLEEP CHANGES INDUCED BY LIPOPOLYSACCHARIDE IN THE RAT DURING THE DARK PERIOD

Sleep is generally enhanced during the early phase of infection. The c ytokine tumor necrosis factor (TNF) has been postulated to play an imp ortant role in the acute phase sleep response. After demonstrating the ability of a soluble p75 TNF receptor (TNFR) to inhibit TNF activity in vitro, we assessed the influence of TNFR on the sleep changes evoke d by lipopolysaccharide (LPS). In this vehicle-controlled experiment, 24 rats received either an intracerebroventricular injection of 10 mu g TNFR, an intraperitoneal injection of 30 mu g/kg LPS, or both, at th e beginning of the dark period. EEG, EMG and brain temperature (T-br) were recorded during the first 12 h post injection. Compared with vehi cle, LPS had minimal effects on T-br, but promoted non-rapid eye movem ent sleep (non-REMS), suppressed REMS, shortened the sleep episodes an d decreased high-frequency (greater than or equal to 8 Hz) EEG activit y during non-REMS. TNFR alone had no significant effects and did not a ttenuate any of the LPS-induced sleep changes. These results may eithe r indicate that TNF is not critically involved in the sleep response t o a low level LPS challenge during the activity phase or that the solu ble p75 TNFR does not effectively antagonize the sleep changes evoked by TNF. (C) 1997 Elsevier Science B.V.