Hypothalamo-pituitary-adrenal axis responses to lipopolysaccharide in male and female rats with adjuvant-induced arthritis.
We have previously demonstrated that rats with adjuvant-induced arthritis (AA) are unable to mount a hypothalamo-pituitary-adrenal (HPA) axis response to either psychological or physical stress. In the present study we have taken male and female rats with AA and injected these with lipopolysaccharide (LPS) as an acute immune challenge and assessed the effects of this challenge at all levels of the HPA axis. We have demonstrated that, in contrast to acute stress, there is an activation of the HPA axis in male AA rats in response to acute immune challenge which occurs at all levels of the HPA axis. The hypothalamic and pituitary response to LPS is intact in the female AA rat. However, there appears to be an impaired adrenal responsiveness in the AA female given LPS. The non-AA female is able to respond to LPS suggesting that this defect is not inherent but is a reaction to the development of inflammation. This hyporesponsiveness has major implications for the ability of the organism to survive infections or immune challenges which are potentially life threatening in the absence of release of anti-inflammatory glucocorticoids from the adrenal cortex. The implications of these changes in the female on the subsequent development of the disease and the mechanisms mediating these effects may provide a better understanding of the gender differences underlying susceptibility to autoimmune diseases.
Harbuz
M S
MS
University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol, United Kingdom, BS2 8HW.
Rooney
C
C
Jones
M
M
Ingram
C D
CD
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology*; D003345:Corticosterone / Q000097:blood; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000473:pathology*; D017403:In Situ Hybridization; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000473:pathology*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone