title: Effects of psychological stress on joint inflammation and adrenal function during induction of arthritis in the Lewis rat.
abstract: Glucocorticoids are effective immunosuppressive and anti-inflammatory agents, but some aspects of stress appear to be proinflammatory. This study investigates this apparent paradox as it applies to stress exposure and the development of arthritis in a rat strain that has subnormal hypothalamic-pituitary-adrenal (HPA) responsiveness. Female Lewis rats were subjected to 1 week of rotating, psychological stressors for 5 h daily, beginning 7 days following inoculation with type II collagen. The collagen-induced arthritis (CIA) group exposed to stress showed reduced ankle width increase (p < 0.001) and decreased hindlimb severity scores (p < 0.001). At sacrifice, 2 days following stress termination, no differences in either measure remained and there was no difference in hind paw volume. However, the area of the tibia invaded by stroma, as quantitated by image analysis, was reduced in the stressed rats (p < 0.05). In animals exposed to stress, adrenal weights were increased (p < 0.005) and plasma corticosterone levels were elevated at sacrifice (p < 0.02). Both injected groups had significantly larger adrenal (p < 0.005) and lower thymus weights (p < 0.05) than did uninjected controls. Likewise, both CIA groups had reduced glucocorticoid receptor immunoreactivity in synovial membranes compared to controls (p < 0.001), suggesting that the Lewis rat's HPA deficiency may be intensified by glucocorticoid receptor downregulation during the induction of CIA. These data indicate that the responsiveness of the HPA axis to psychological stress in this strain is sufficient to alter disease progression.
authors.affiliation: Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0576, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Miller
authors.forename: S H
authors.initials: SH
authors.lastname: Rapier
authors.forename: L I
authors.initials: LI
authors.lastname: Holtsclaw
authors.forename: B B
authors.initials: BB
authors.lastname: Turner
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D003094:Collagen / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D005260:Female; D006614:Hindlimb / Q000503:physiopathology; D006651:Histocytochemistry; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*; D013583:Synovial Membrane / Q000378:metabolism; D013643:Tarsus, Animal / Q000276:immunology* / Q000503:physiopathology
chemical_list: D011965:Receptors, Glucocorticoid; D003094:Collagen; D003345:Corticosterone