The hypothalamic-pituitary-adrenal axis in autoimmunity.
We have characterized the activation of the HPA axis in the chronic inflammatory stress model of adjuvant-induced arthritis. Alteration in the hypothalamic control mechanism, where CRF is no longer the major corticotrophin-releasing factor, has been noted in a number of other immune-mediated disease models, including experimental allergic encephalomyelitis, eosinophilia myalgia syndrome, systemic lupus erythematosus, and leishmaniasis. These changes occur in both the mouse and the rat, suggesting this may be a common mechanism to chronic immune activation. We have good evidence to suggest that AVP takes over as the major stimulator of the axis. The arthritic rat is unable to mount a response to acute stressors, such as restraint or ip hypertonic saline. However, these animals are able to mount a response to an acute immune challenge. These data provide further evidence for a differential activation of the HPA by acute stress or acute immune stimulation. This presumably reflects an adaptive response to the development of chronic inflammation. We have demonstrated that central neurotransmitter systems are able to influence the severity of peripheral inflammation. In particular we have shown that depletion of serotonin at the time of the development of the inflammatory episode reduces the severity of the inflammation. These findings suggest the possibility of novel therapeutic strategies targeting neurotransmitter systems to alleviate inflammation.
Harbuz
M S
MS
Department of Hospital Medicine, Bristol Royal Infirmary, United Kingdom. m.s.harbuz@bris.ac.uk
Conde
G L
GL
Marti
O
O
Lightman
S L
SL
Jessop
D S
DS
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000503:physiopathology*; D002908:Chronic Disease; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology; D009490:Neurosecretory Systems / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D013312:Stress, Physiological / Q000503:physiopathology