PENTOXIFYLLINE INHIBITS TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA)-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 mecha nisms. Because cell adhesion to endothelial cells is a critical step i n the initiation of such immune responses, we analyzed whether pentoxi fylline would affect this process. To address this issue, adhesion of mouse T-lymphoma cells (TK-1) to mouse endothelioma cells (eEnd.2), ei ther untreated or stimulated with tumor necrosis factor-alpha (TNF alp ha), was studied. Pentoxifylline reduced the ability of endothelioma c ells stimulated with different concentrations of TNF alpha, but not of untreated endothelioma cells, to bind T-lymphoma cells in dose-depend ent (10(-5)-10(-3) M) fashion, Selective incubation of either endothel ioma cells or T-lymphoma cells revealed that pentoxifylline acted excl usively on the endothelioma cells, even when added after TNF alpha sti mulation, We questioned whether pentoxifylline suppressed T-lymphoma c ell/ endothelioma cell interactions by interfering with adhesion molec ules expressed by either cell. However, as determined by flow cytometr y, pentoxifylline did not alter TNF alpha-induced upregulation of inte rcellular adhesion molecule-1 or vascular cellular adhesion molecule-1 on endothelioma cells nor did it affect constitutive CD11a, CD18, or alpha 4-integrin expression on T-lymphoma cells, suggesting that rathe r than affecting quantitative expression of these adhesion molecules, pentoxifylline might modulate their avidity. Fire conclude that pentox ifylline in therapeutically achievable concentrations is a potent inhi bitor of TNF alpha-induced T-lymphoma cell adhesion to endothelioma ce lls. This finding may account, at least in part, for the recently disc overed anti-inflammatory action of pentoxifylline.