PMID- 8655288 OWN - NLM STAT- MEDLINE DCOM- 19960801 LR - 20190920 IS - 0162-3109 (Print) IS - 0162-3109 (Linking) VI - 31 IP - 1 DP - 1995 Nov TI - Methylxanthines with adenosine alter TNF alpha-primed PMN activation. PG - 19-29 AB - Methylxanthines are best known as phosphodiesterase inhibitors that cause a rise in intracellular cAMP. One would expect the two methylxanthines, caffeine and pentoxifylline, to have similar actions on neutrophils (PMN). However, caffeine stimulated and pentoxifylline inhibited PMN oxidative activity. Micromolar concentrations of pentoxifylline decreased native and recombinant tumor necrosis factor-alpha (TNF alpha)-primed formyl met-leu-phe (fMLP)-stimulated PMN chemiluminescence, superoxide production and myeloperoxidase (MPO) release. In contrast, equal concentrations of caffeine increased chemiluminescence and MPO release with no effect on superoxide production. These activities of the methylxanthines were only observed in the presence of physiological concentrations of adenosine, and were abolished by the treatment of the PMN with adenosine deaminase. The activities of adenosine, pentoxifylline and caffeine on PMN activity could not be readily explained by changes in PMN [cAMP]. Thus for TNF alpha-primed PMN, pentoxifylline decreases PMN activity by enhancing the effect of adenosine on degranulation and superoxide production; whereas caffeine increases PMN activity by counteracting the effect of adenosine on degranulation. FAU - Sullivan, G W AU - Sullivan GW AD - Department of Medicine, University of Virginia, Charlottesville 22908, USA. FAU - Luong, L S AU - Luong LS FAU - Carper, H T AU - Carper HT FAU - Barnes, R C AU - Barnes RC FAU - Mandell, G L AU - Mandell GL LA - eng GR - AI09504/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Immunopharmacology JT - Immunopharmacology JID - 7902474 RN - 0 (Tumor Necrosis Factor-alpha) RN - 11062-77-4 (Superoxides) RN - 3G6A5W338E (Caffeine) RN - EC 1.11.1.7 (Peroxidase) RN - K72T3FS567 (Adenosine) RN - SD6QCT3TSU (Pentoxifylline) SB - IM MH - Adenosine/*pharmacology MH - Caffeine/*pharmacology MH - Humans MH - Kinetics MH - Luminescent Measurements MH - *Neutrophil Activation MH - Neutrophils/*drug effects/*metabolism MH - Pentoxifylline/*pharmacology MH - Peroxidase/metabolism MH - Superoxides/metabolism MH - Tumor Necrosis Factor-alpha/immunology EDAT- 1995/11/01 00:00 MHDA- 1995/11/01 00:01 CRDT- 1995/11/01 00:00 PHST- 1995/11/01 00:00 [pubmed] PHST- 1995/11/01 00:01 [medline] PHST- 1995/11/01 00:00 [entrez] AID - 0162310995000300 [pii] AID - 10.1016/0162-3109(95)00030-0 [doi] PST - ppublish SO - Immunopharmacology. 1995 Nov;31(1):19-29. doi: 10.1016/0162-3109(95)00030-0.