Pentoxifylline Inhibits Tumor Necrosis Factor-α (TNFα)-Induced T-Lymphoma Cell Adhesion to Endothelioma Cells

Pentoxifylline, a methylxanthine derivative, has been shown to inhibit T-cell-mediated cutaneous immune response by yet ill-understood mechanisms, Because cell adhesion to endothelial cells is a critical step in the initiation of such immune responses, we analyzed whether pentoxifylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), either untreated or stimulated with tumor necrosis factor-α (TNFα), was studied. Pentoxifylline reduced the ability of endothelioma cells stimulated with different concentrations of TNFα, but not of untreated endotheliotna cells, to bind T4ymphozna cells in dose-dependent (10 –5 –10 –3 M) fashion. Selective incubation of either endothelioma cells or T- lymphoma cells revealed that pentoxifylline acted exclusively on the endothelioma cells, even when added after TNFα stimulation. We questioned whether pentoxifylline suppressed T-lyznphoma edit endothelioma cell interactions by interfering with adhesion molecules expressed by either cell. However, as determined by flow cytometry, pentoxifylline did not alter TNFα-induced upregulation of intercellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or α4-integrin expression on T-lymphoma cells, suggesting that rather than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. We conclude that pentoxifylline in therapeutically achievable concentrations is a potent inhibitor of TNFα-induced T-lymphoma cell adhesion to endothelioma cells. This finding may account, at least in part, for the recently discovered anti-inflammatory action of pentoxifylline.