Growth hormone-releasing hormone and interleukin-1 in sleep regulation

Growth hormone-releasing hormone (GHRH) and interleukin-1 (IL-1) are putative endogenous sleep-promoting substances. Evidence is reviewed showing that, 1) GHRH and IL-1 promote non-rapid eye movement sleep (NREMS); 2) if their production is enhanced, sleep is enhanced; and 3) if they are inhibited using either specific antibodies or peptide antagonists, sleep is reduced. Both are in the brain and both are also indirectly linked to sleep/wake cycles by various other evidence, e.g., growth hormone release and IL-1 plasma levels vary in phase with sleep/wake cycles. Finally, their actions are directly linked to each other; e.g., IL-1-induced growth hormone release is mediated via GHRH. The evidence reviewed strongly implicates both GHRH and IL-1 as key components in humoral sleep regulation. Humoral theories of sleep regulation are complementary to neural theories; both mechanisms affect each other and undoubtedly continuously interact to regulate sleep/wake cycles.