NEUTROPHIL TRAFFICKING INTO INFLAMED JOINTS IN PATIENTS WITH RHEUMATOID-ARTHRITIS, AND THE EFFECTS OF METHYLPREDNISOLONE

Objective. To investigate the trafficking of circulating blood neutrop hils and synovial fluid neutrophils in rheumatoid arthritis (RA) patie nts and the influence of a 1,000-mg intravenous pulse of methylprednis olone succinate (MP). Methods. Neutrophils were isolated from the circ ulation and from the knee synovial compartments of subjects with RA. C irculating neutrophils were labeled with technetium-99m hexametazime T c-99m-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled with indium-111 oxine and reinjected into the knee from w hich they were isolated. Gamma camera images were obtained at interval s up to 24 hours post MP. Each patient had a baseline study (no MP) an d a study in which MP was administered either 4 hours before (2 patien ts), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after ( 6 patients) injection of the radiolabeled neutrophils. Subsequent anal ysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time. Results. Nine patients who had no t received glucocorticoids in the previous 3 months were studied. MP s ignificantly decreased neutrophil ingress in 13 of the 16 knees studie d (almost total inhibition in 5 knees), and this occurred within 1.5 h ours of MP administration in all except 1 knee. At 24 hours after MP a dministration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on th e modified Health Assessment Questionnaire (P < 0.05), tender joints ( P < 0.005), VAS for pain (P < 0.005), and generalized stiffness (P < 0 .005), as well as a decrease in the C-reactive protein level (P < 0.05 ). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no e ffect on neutrophil ingress. The other patient showed no neutrophil in gress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis. Conclusion. Neutr ophil ingress into and egress from inflamed joints can be accurately m onitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress int o inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.