The effect of anti-inflammatory agents and inflammation on granulocyte adherence. Evidence for regulation by plasma factors

Abstract

Significant inhibition of granulocyte adherence to nylon fiber columns followed the administration of alcohol, aspirin, sodium salicylate, acetaminophen, indomethacin, phenylbutazone, colchicine or prednisone to normal subjects. The addition of salicylates and glucocorticoids to blood in vitro had no effect on adherence, but plasma from volunteer subjects treated with either drug contained a factor which inhibited the adherence of normal granulocytes. The factor is heat stable, nondialyzable and not present in serum; it produces a linear dose response in normal cells. When mixed with the adherence-increasing factor found in inflammatory diseases, it neutralizes the augmenting effect and normal granulocyte adherence results. The effect of anti-inflammatory therapy on inflammatory disease was studied in aspirin-treated patients with rheumatoid arthritis. Their granulocyte adherence fell into two categories based on the clinical control of their disease; patients in good control had only slightly increased granulocyte adherence, but those in poor control had an average adherence more than twice normal. Mean blood aspirin levels were equivalent for the two groups (11.0 mg/100 ml for the well controlled and 13.4 mg/100 ml for those poorly controlled). Thus, clinical response to anti-inflammatory therapy correlates well with granulocyte adherence, not with aspirin levels. The potential pathogenetic role of adherence-modifying factors in inflammatory diseases remains to be determined.