Exacerbation of adjuvant arthritis by adrenalectomy is associated with reduced leukocyte lipocortin 1.
OBJECTIVE
Lipocortin 1 is a mediator of the antiinflammatory actions of therapeutic glucocorticoids. ENdogenous glucocorticoids modulate inflammatory arthritides including rheumatoid and adjuvant arthritis (AA), but the role of lipocortin 1 in this phenomenon is not known. We studied the effects of endogenous glucocorticoids on adjuvant arthritis and leukocyte lipocortin 1 content.


METHODS
Adrenalectomy of sham adrenalectomy was performed 2 days before adjuvant injection in 170 g inbred Sprague-Dawley rats. Peripheral blood was obtained and disease severity assessed by delta paw volume and clinical score 14 days later. Leukocyte subset lipocortin 1 content was determined by double labeling permeabilization flow cytometry using specific monoclonal antibodies.


RESULTS
Lipocortin 1 fluorescence was readily detected in control rat peripheral blood cells labeled with OX-1 (pan-leukocyte), OX-19 (CD5), W3/25 (CD4), and OX-8 (CD8). Lipocortin 1 fluorescence was significantly greater in polymorphonuclear leukocytes (PMN) (RP3; p < 0.01). Induction of AA was accompanied by significant increases in lipocortin 1 (p < 0.001) in all subsets. Sham adrenalectomy induced no significant change in AA rat leukocyte lipocortin 1. Adrenalectomy induced significant exacerbation of AA disease severity compared to sham operation (delta paw volume 1.43 +/- 0.1 vs 1.13 +/- 0 ml; p < 0.05). Adrenalectomy was also associated with significant reduction in lipocortin 1 content in all leukocyte subsets except PMN. Leukocyte lipocortin 1 content exhibited significant negative correlation with clinical disease severity (R2 = -0.55; p < 0.05).


CONCLUSIONS
Endogenous glucocorticoids modulate leukocyte expression of lipocortin 1 in inflammatory disease, and reduced lipocortin 1 may be involved in the exacerbation of AA by adrenalectomy.
Yang
Y H
YH
Centre for Inflammatory Diseases, Monash Medical Centre, Monash University, Victoria, Australia.
Hutchinson
P
P
Leech
M
M
Morand
E F
EF
D000315:Adrenalectomy / Q000009:adverse effects*; D000818:Animals; D017305:Annexin A1 / Q000097:blood / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000209:etiology* / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005121:Extremities / Q000473:pathology; D005434:Flow Cytometry; D007962:Leukocytes / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D017305:Annexin A1