Analysis of adrenocortical secretory responses during acute an prolonged immune stimulation in inflammation-susceptible and -resistant rat strains.
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 beta-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 beta-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, beta-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 beta-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 beta-glucan-challenged DA rats whereas resistance to inflammation in PVG.1AV1 rats may be mediated via corticosterone-independent mechanisms.
Andersson
I M
IM
Department of Medicine, Unit of Rheumatology, Karolinska Institute, Stockholm, Sweden. ingela.andersson@cmm.ki.se
Lorentzen
J C
JC
Ericsson-Dahlstrand
A
A
D000302:Adrenal Cortex / Q000378:metabolism*; D000315:Adrenalectomy; D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000503:physiopathology; D003345:Corticosterone / Q000378:metabolism; D004926:Escherichia coli; D020022:Genetic Predisposition to Disease; D005936:Glucans / Q000008:administration & dosage / Q000276:immunology; D005938:Glucocorticoids / Q000502:physiology; D007031:Hypothalamus / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008099:Liver / Q000737:chemistry; D008297:Male; D010902:Pituitary Gland / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D014156:Transcortin / Q000235:genetics
D005936:Glucans; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014156:Transcortin; D003345:Corticosterone