Effects of pentoxifylline administration on blood viscosity and leukocyte cytoskeletal function in patients with intermittent claudication.

We have previously shown that pentoxifylline, a drug used in intermittent claudication, causes depolymerization of actin in leukocytes in vitro. In this study we evaluated several parameters in peripheral blood obtained from 17 patients receiving pentoxifylline, before therapy and at 1 and 2 months after initiation of drug therapy. Total blood viscosity decreased at 1 month and was further reduced at 2 months. The plasma viscosity remained unchanged during the course of the therapy (1.770 +/- 0.147, 1.776 +/- 0.162, and 1.772 +/- 0.164 centipoise at 0, 1, and 2 months, respectively; mean +/- SD, n = 14 to 17). No changes were observed in stimulus-induced actin polymerization in granulocytes, concanavalin A-induced capping in granulocytes and lymphocytes, and anti-IgG-induced caps in lymphocytes, before and after therapy. Similarly, there was no difference in the magnitude of depolymerization caused by pentoxifylline when added in vitro. Thus none of the parameters altered by pentoxifylline treatment in vitro have been observed ex vivo in patients receiving this drug. However, the decrease in total blood viscosity along with unaltered plasma viscosity suggests that the rheology of the cellular elements is being affected by the administered drug. In addition to the direct effects on the cell membrane and the cytoskeleton, pentoxifylline may exert indirect effects through its inhibitory action on cytokine production. Subtle changes in a number of parameters in leukocytes, which taken alone fail to show demonstrable changes, might ultimately be responsible for the therapeutic benefit noted with pentoxifylline.