Humoral regulation of physiological sleep: cytokines and GHRH

Interleukin-1, tumour necrosis factor, and growth hormone releasing hormone form part of the humoral mechanisms regulating physiological sleep. Their injection enhances non-rapid-eye-movement sleep whereas their inhibition re duces spontaneous sleep and sleep rebound after sleep deprivation. Changes in their mRNA levels and changes in their protein levels in the brain are c onsistent within their proposed role in sleep regulation. Furthermore, resu lts from transgenic and mutant animals also are suggestive of their role in sleep regulation. The sites responsible for the growth hormone releasing h ormone somnogenic activity seem to reside in the anterior hypothalamus/basa l forebrain. Somnogenic sites for interleukin-l and tumour necrosis factor likely include the anterior hypothalamus, but also may extend beyond that a rea. These substances elicit non-rapid-eye-movement sleep via a biochemical cascade that includes other known sleep regulatory substances.