Circadian Organization of the Immune Response: Rat Adjuvant Arthritis as a Model

Abstract

This chapter discusses the circadian disruption of hormone release and immune-related mechanisms in the rat adjuvant arthritis model. The experimental manipulation used perturbed the temporal organization by affecting the shape and amplitude of the rhythm. Although circadian rhythms are anchored genetically, they are synchronized by and maintain certain phase relationships to external factors. In mammals, the circadian system is composed of many individual, tissue-specific cellular clocks. To generate coherent physiological and behavioral responses, a master circadian pacemaker orchestrates the phases of a multitude of cellular clocks. This circadian pacemaker resides in the suprachiasmatic nuclei (SCN) of the hypothalamus. At a molecular level, circadian clocks are based on clock genes, some of which encode proteins able to feed back and inhibit their own transcription. The daily variation of biological variables arises from an internal time-keeping system, and the major action of the environment is to synchronize this internal clock to a period of exactly 24 hours. The light–dark cycle, food, ambient temperature, scents, and social cues have been identified as environmental synchronizers or “Zeitgebers” in rats. Further experiments are needed to assess whether the changes in amplitude, as well in the timing of 24-hour rhythms discussed herein, can be attributed to an effect on the SCN or to a masking effect on some output(s) of the clock.