Total and partial sleep deprivation: Effects on plasma TNF-αRI, TNF-αRII, and IL-6, and reversal by caffeine operating through adenosine A2 receptor

Abstract

Plasma levels of IL-6 and TNF-α are elevated in individuals who are deprived of sleep. TNF-α regulates expression of its soluble receptors, sTNF-αRI and sTNF-αRII. Sleep deprivation (SD) also increases extracellular adenosine that induces sedation and sleep. An antagonist of adenosine, caffeine, raises exogenous adenosine levels, stimulates the expression of IL-6 and inhibits the release of TNF-α. Our objective was to determine the effect of total SD (TSD) or partial SD (PSD) on the levels of these sleep regulatory molecules in volunteers who experienced SD with or without the consumption of caffeine. Plasma levels of IL-6, sTNF-αRI and sTNF-αRII were assayed by ELISA in samples collected at 90-min intervals from each subject over an 88-hour period. The results were analyzed by the repeated measures ANOVA. Whereas only TSD significantly increased sTNF-αRI over time, caffeine suppressed both sTNF-α receptors in TSD and PSD subjects. The selective increase in the expression of sTNF-αRI and not sTNF-αRII in subjects experiencing TSD with caffeine compared with others experiencing PSD with caffeine has not been previously reported. Moreover, caffeine significantly increased IL-6 in TSD subjects compared with those who did not receive caffeine. However, subjects who were permitted intermittent naps (PSD) ablated the effects of caffeine and reduced their level of IL-6 to that of the TSD group. These data further lend support to the hypothesis that the sTNF-αRI and not the sTNF-αRII plays a significant role in sleep regulation by TNF-α.