Effects of cyclosporine A on the hypothalamic-pituitary-adrenal axis and anterior pituitary interleukin-6 mRNA expression during chronic inflammatory stress in the rat.
In the rat, adjuvant arthritis (AA) is an inflammatory joint disease associated with chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. We have investigated the effects of the immunosuppressive agent cyclosporine A (CsA) on plasma levels of adrenocorticotropin (ACTH) and corticosterone (B), as well as on anterior pituitary proopiomelanocortin (POMC) and interleukin (IL)-6 mRNA accumulation in control and adjuvant-injected animals. In control animals, CsA reduced basal anterior pituitary POMC and IL-6 mRNA and decreased plasma levels of ACTH and B. Adjuvant-injected animals that were treated with CsA showed no clinical signs of AA. Moreover, CsA inhibited the arthritis-induced increases in pituitary POMC and IL-6 mRNA levels and in circulating ACTH and B. In vitro, CsA reduced the POMC mRNA content of cultured anterior pituitary cells and diminished the stimulatory effects of corticotropin-releasing hormone (CRH) on POMC mRNA expression and ACTH secretion from these cells. These data indicate that CsA has a direct action on the HPA axis and also reduces the activation of the HPA axis seen in chronic inflammatory arthritis.
Stephanou
A
A
Neuroendocrinology Unit, Charing Cross and Westminster Medical School, Charing Cross Hospital, London, UK.
Sarlis
N J
NJ
Knight
R A
RA
Lightman
S L
SL
Chowdrey
H S
HS
D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D002908:Chronic Disease; D016572:Cyclosporine / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015850:Interleukin-6; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D016572:Cyclosporine; D000324:Adrenocorticotropic Hormone