Exacerbation of adjuvant arthritis by adrenalectomy is associated with reduced leukocyte lipocortin 1.

Abstract

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 or 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 A 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). Conclusion. 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.