Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha and TNF-alpha fragments

Abstract

Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of generalized infections such as fever, increased sleep, and anorexia. The aim of the present work was to localize these effects of TNF-alpha to specific amino acid sequences of the parent molecule by characterizing the in vivo and in vitro activities of several synthetic TNF-alpha fragments. Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited monophasic fevers. All of the somnogenic fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF-alpha increased the expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell line. In contrast, none of the fragments possessed these in vitro activities. Our in vivo results support the concept that there are biologically active regions in the TNF-alpha molecule.

Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

“…Consistent with current results, they affect each other's production and inhibition of one attenuates the sleep induced by the other (Takahashi et al, 1999. Low doses of IL1β or TNFα enhance non rapid eye movement sleep (NREMS) (Kapas et al, 1992;Krueger et al, 1984;Shoham et al, 1987;Tobler et al, 1984). Conditions associated with increases in endogenous levels of IL1β or TNFα, e.g., time-of-day (Floyd and Krueger, 1997;Taishi et al, 1998), excessive food intake or infectious disease (Toth and Krueger, 1988) promote NREMS.…”

Relationship between sleep duration and the metabolic syndrome: Korean National Health and Nutrition Survey 2001

“…Previous studies have demonstrated that subjects in the sleep-deprived state have impaired glucose tolerance, higher evening cortisol levels, increased sympathetic nervous system activity and a reduction in leptin secretion compared to those in the recovery state. 30 Although mechanisms underlying the association between long sleep duration and diabetes are unclear, chronic subclinical inflammation associated with visceral obesity may trigger long sleep duration and hyperglycemia due to the sleep-inducing 31 and metabolic 32 effects of pro-inflammatory cytokines, including interleukin-1 and tumor necrosis factor-a. Blood pressure gradually falls with the onset of sleep, and promptly rises after awakening.…”

Sleep Apnea and its Association with the Stress System, Inflammation, Insulin Resistance and Visceral Obesity

“…In normal people the inflammatory cytokines tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and interleukin-6 (IL-6) are involved in physiological sleep regulation with a circadian pattern of secretion (25)(26)(27)(28). Decreased overall secretion of IL-6 is associated with a good night's sleep and a good sense of well-being the next day (27).…”