A two-clock model of circadian timing in the immune system of mammals.

It has been confirmed that clock genes, as well as the pineal hormone, have a role in the hypothalamic suprachiasmatic nucleus, the circadian endogenous pacemaker. It seems that the peripheral clock genes in the cells of the immune system subtly control biorhythms; their seeming lack of impact only showing that they work well. Some biorhythms even seem to be independent of a light/dark circadian regime. This apparent conflict in the mammalian time structure can be resolved by a two-clocks control model involving: (a) the endogenous gene clock, which is dominant in the neural system and (b) the exogenous clock of the immune system. Interactions between these two clocks can explain both the frequently observed individual differences in circadian rhythms and the subtle role of the peripheral clock genes. The endogenous clock facilitates an alternation in the immune system which counters external attacks in daytime and induces repair and advancement by night.