Effects of pentosan polysulfate on peripheral blood leukocyte populations and mononuclear cell procoagulant activity in patients with osteoarthritis

Abstract

Pentosan polysulfate (PPS) is a new antiarthritis drug whose mechanism of action is still under investigation. The objective of this study was to determine the effects of PPS on peripheral blood mononuclear cell procoagulant activity (MPA) and individual blood leukocyte populations in 11 patients with osteoarthritis (OA) before treatment, over 24 hours, and 4 weeks after four weekly intramuscular injections (3 mg/kg) of the drug. In all patients, MPA was reduced statistically significantly, relative to baseline values, for up to 24 hours after a single PPS injection. However, in those patients with moderate OA (Kellgren and Lawrence, grade 2), this reduction in MPA was significantly sustained for up to 4 weeks after the last injection of PPS. Following the initial PPS injection the levels of circulating leukocytes increased in the blood of all OA patients, reaching a maximum after 8 hours. The major cellular contribution to this elevation was from lymphocytes, because monocyte levels initially decreased and neutrophils remained unchanged. Four weeks after the last of the four PPS injections, lymphocyte populations were still significantly increased, whereas neutrophils and monocyte levels were decreased in the majority of patients compared with their baseline values. Although platelet levels remained unchanged during the initial 24 hours after PPS injection, a small but statistically significant increase was observed 4 weeks after the last injection. These data demonstrate the ability of PPS to selectively recruit lymphocytes into the circulation and modulate the expression of MPA. We suggest that these activities may contribute to the mechanism of action of the drug.