EFFECT OF PENTOXIFYLLINE ON NITRIC-OXIDE RELEASED BY MURINE MACROPHAGES

The growing knowledge on the pathological role of tumor necrosis facto r alpha (TNF-alpha) and nitric oxide in septic shock stimulated effort s to control their generation pharmacologically in clinical stuations. Pentoxifylline (PTXF) is well known as an inhibitor of TNF synthesis, whereas information about its role in suppression of NO generation is much less available. In our study, we have shown that PTXF suppresses the synthesis of both mediators, TNF and NO, released by macrophages activated with different stimuli. However, in contrast to N-monomethyl -L-arginine (an inhibitor of NO synthase), PTXF influenced NO generati on only during the induction phase. In conclusion, we suggest that a p ossible new therapeutic approach in septic shock may result from the i nhibition of these two major mediators by simultaneous application of PTXF and a specific inhibitor of NO generation. Further experimental i nvestigations and clinical trials are necessary to evaluate the safety and effectiveness of application of these inhibitors.