Analysis of Adrenocortical Secretory Responses During Acute and Prolonged Immune Stimulation in Inflammation‐Susceptible and‐Resistant Rat Strains

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Abstract
Endogenous corticosterone secreted during immune challenge restricts the inflammatory process and genetic variations in this neuroendocrine–immune dialogue have been suggested to influence an individuals sensitivity to develop chronic inflammatory disorders. We have tested inflammation‐susceptible Dark Agouti (DA) rats and resistant, MHC‐identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bacterial lipopolysaccharide (LPS) or a prolonged activation of the nonspecific immune system with arthritogenic yeast β‐glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strains. Interestingly, peak concentrations of corticosterone did not differ significantly between the strains. Intradermal injection of β‐glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of plasma from glucan‐injected DA and PVG.1AV1 rats did not reveal elevated concentrations of plasma corticosterone at any time from days 1–30 postinjection compared to preinjection values, in spite of the ongoing inflammatory process. Interestingly, adrenalectomized, β‐glucan‐challenged DA rats responded with an aggravated arthritic process, indicating an anti‐inflammatory role for the basal levels of corticosterone that were detected in intact DA rats challenged with β‐glucan. Moreover, substitution with subcutaneous corticosterone‐secreting pellets, yielding moderate stress‐levels, significantly attenuated the arthritic response. In contrast, adrenalectomized and glucan‐challenged PVG.1AV1 rats did not respond with an elevated arthritic response, suggesting that these rats contain the arthritic process via corticosterone‐independent mechanisms. In conclusion, the hypothalamic‐pituitary‐adrenal axis in both rat strains exhibited strong activation after challenge with LPS. This contrasted to the basal corticosterone levels observed strains during a prolonged arthritic process. No correlation between ability to secrete corticosterone and susceptibility to inflammation could be demonstrated. Basal levels of endogenous corticosterone appeared to restrain inflammation in β‐glucan‐challenged DA rats whereas resistance to inflammation in PVG.1AV1 rats may be mediated via corticosterone‐independent mechanisms.