EFFECT OF NEOPTERIN AND 7,8-DIHYDRONEOPTERIN ON TUMOR-NECROSIS-FACTOR-ALPHA INDUCED PROGRAMMED CELL-DEATH

Tumor necrosis factor-alpha and the formation of reactive oxygen inter mediates are central mediators of apoptosis. Recent data indicated a r ole of neopterin and 7,8-dihydroneopterin in oxygen radical mediated p rocesses. We have therefore investigated the effect of neopterin-deriv atives on TNF alpha induced apoptosis of the monocyte-like cell line U 937. At an elevated concentration 7,8-dihydroneopterin was found to su perinduce TNF alpha mediated programmed cell death due to the formatio n of reactive oxygen intermediates. Our results imply that in combinat ion with TNF alpha high concentrations of 7,8-dihydroneopterin enhance s apoptosis due to oxidative stress on cells.