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 cytokine tumor necrosis factor (TNF) has been postulated to play an important 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 evoked by lipopolysaccharide (LPS). In this vehicle-controlled experiment, 24 rats received either an intracerebroventricular injection of 10 micrograms TNFR, an intraperitoneal injection of 30 micrograms/kg LPS, or both, at the beginning of the dark period. EEG, EMG and brain temperature (Tbr) were recorded during the first 12 h post injection. Compared with vehicle, LPS had minimal effects on Tbr, but promoted non-rapid eye movement sleep (non-REMS), suppressed REMS, shortened the sleep episodes and decreased high-frequency (> or = 8 Hz) EEG activity during non-REMS. TNFR alone had no significant effects and did not attenuate any of the LPS-induced sleep changes. These results may either indicate that TNF is not critically involved in the sleep response to a low level LPS challenge during the activity phase or that the soluble p75 TNFR does not effectively antagonize the sleep changes evoked by TNF.
Lancel
M
M
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany. lancel@mpipsykl.mpg.de
Mathias
S
S
Schiffelholz
T
T
Behl
C
C
Holsboer
F
F
D000818:Animals; D001143:Arousal / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature; D001921:Brain / Q000502:physiology; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000139:chemically induced; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D012995:Solubility; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha