EFFECTS OF PENTOSAN POLYSULFATE ON PERIPHERAL-BLOOD LEUKOCYTE POPULATIONS AND MONONUCLEAR CELL PROCOAGULANT ACTIVITY IN PATIENTS WITH OSTEOARTHRITIS

Pentosan polysulfate (PPS) is a new antiarthritis drug whose mechanism of action is still under investigation. The objective of this study w as to determine the effects of PPS on peripheral blood mononuclear cel l procoagulant activity (MPA) and individual blood leukocyte populatio ns in 11 patients with osteoarthritis (OA) before treatment, over 24 h ours, and 4 weeks after four weekly intramuscular injections (3 mg/kg) of the drug. In all patients, MPA was reduced statistically significa ntly, relative to baseline values, for up to 24 hours after a single P PS injection. However, in those patients with moderate OA (Kellgren an d Lawrence, grade 2), this reduction in MPA was significantly sustaine d for up to 4 weeks after the last injection of PPS. Following the ini tial PPS injection the levels of circulating leukocytes increased in t he blood of all OA patients, reaching a maximum after 8 hours. The maj or cellular contribution to this elevation was from lymphocytes, becau se monocyte levels initially decreased and neutrophils remained unchan ged. Four weeks after the last of the four PPS injections, lymphocyte populations were still significantly increased, whereas neutrophils an d monocyte levels were decreased in the majority of patients compared with their baseline values. Although platelet levels remained unchange d during the initial 24 hours after PPS injection, a small but statist ically significant increase was observed 4 weeks after the last inject ion. These data demonstrate the ability of PPS to selectively recruit lymphocytes into the circulation and modulate the expression of MPA. W e suggest that these activities may contribute to the mechanism of act ion of the drug.