Analysis of adrenocortical secretory responses during acute and prolonged immune stimulation in inflammation-susceptible and -resistant rat strains

Endogenous corticosterone secreted during immune challenge restricts the in flammatory process and genetic variations in this neuroendocrine-immune dia logue have been suggested to influence an individuals sensitivity to develo p chronic inflammatory disorders. We have tested inflammation-susceptible D ark Agouti (DA) rats and resistant, MHC-identical, PVG.1AV1 rats for their abilities to secrete corticosterone in response to acute challenge with bac terial lipopolysaccharide (LPS) or a prolonged activation of the nonspecifi c immune system with arthritogenic yeast beta-glucan. Intravenous injection of LPS triggered equipotent secretion of corticosterone in both rat strain s. Interestingly, peak concentrations of corticosterone did not differ sign ificantly between the strains. Intradermal injection of beta-glucan caused severe, monophasic, polyarthritis in DA rats while PVG.1AV1 responded with significantly milder joint inflammation. Importantly, serial sampling of pl asma from glucan-injected DA and PVG.1AV1 rats did not reveal elevated conc entrations of plasma corticosterone at any time from days 1-30 postinjectio n compared to preinjection values, in spite of the ongoing inflammatory pro cess. Interestingly, adrenalectomized, beta-glucan-challenged DA rats respo nded 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 beta-glucan. Moreover, substitution with subcutaneous corticosterone-secreting pellets, yielding moderate stress-levels, signifi cantly 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 cor ticosterone-independent mechanisms. In conclusion, the hypothalamic-pituita ry-adrenal axis in both rat strains exhibited strong activation after chall enge with LPS. This contrasted to the basal corticosterone levels observed strains during a prolonged arthritic process. No correlation between abilit y to secrete corticosterone and susceptibility to inflammation could be dem onstrated. Basal levels of endogenous corticosterone appeared to restrain i nflammation in beta-glucan-challenged DA rats whereas resistance to inflamm ation in PVG.1AV1 rats may be mediated via corticosterone-independent mecha nisms.