Hypothalamo-pituitary-adrenal axis responses to lipopolysaccharide in maleand 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 t aken male and female rats with AA and injected these with lipopolysaccharid e (LPS) as an acute immune challenge and assessed the effects of this chall enge 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 ax is. 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 sugges ting that this defect is not inherent but is a reaction to the development of inflammation. This hyporesponsiveness has major implications for the abi lity of the organism to survive infections or immune challenges which are p otentially 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 mechanis ms mediating these effects may provide a better understanding of the gender differences underlying susceptibility to autoimmune diseases. (C) 1999 Aca demic Press.