BIPHASIC CHANGES IN BEHAVIORAL, ENDOCRINE, AND SYMPATHETIC SYSTEMS INADJUVANT ARTHRITIS IN LEWIS RATS

Adjuvant arthritis (AA) is an experimental model for rheumatoid arthri tis, and is induced most easily in inbred Lewis rats by an intradermal injection of heat-killed Mycobacterium tuberculosis (MT) in incomplet e Freund's adjuvant. Susceptivity to the arthritis in Lewis rats is th ought to be related to a defect in their responses of the hypothalamo- pituitary-adrenal (HPA) axis to the disease. Because the use of an inb red strain is necessary for our immunological studies, we examined in Lewis rats changes in behavior, the HPA axis, and sympathetic nerve ac tivities during development of the adjuvant arthritis. Following intra dermal injections of heat-killed MT in adjuvant, the arthritis began t o develop on day 12, reaching its maximum severity on day 21, and rema ined at the level for over a month. The body temperature rose from day 0 to 5 (the primary phase-before the onset of the arthritis). It then fell to normal temperature, and again rose from day 10 to 21 (the sec ondary phase-with fully developed arthritis). The behavioral (physical activity, food, and water intake) and hormonal parameters [plasma adr enocorticotropic hormone (ACTH) and corticosterone levels] also change d in two phases, similar to those observed in the temperature response s. No change in plasma vasopressin level was observed. Sympathetic ner ve activities, assessed by changes in plasma noradrenalin levels, incr eased more in the primary than in the secondary phase. The possible ca uses for the biphasic changes associated with development of arthritis are discussed.