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Methylxanthines with adenosine alter TNF alpha-primed PMN activation
G W Sullivan1, L S Luong, H T Carper
1Department of Medicine, University of Virginia, Charlottesville 22908, USA.
Immunopharmacology
|November 1, 1995
Summary
Caffeine and pentoxifylline, both methylxanthines, have opposing effects on neutrophil activity. Pentoxifylline inhibits, while caffeine stimulates, neutrophil responses, particularly in the presence of adenosine.
Area of Science:
- Immunology
- Pharmacology
Background:
- Methylxanthines like caffeine and pentoxifylline are known phosphodiesterase inhibitors.
- They are expected to have similar effects on neutrophils (PMN) due to their mechanism of action.
Purpose of the Study:
- To investigate the differential effects of caffeine and pentoxifylline on neutrophil (PMN) oxidative activity.
- To elucidate the role of adenosine in mediating these methylxanthine effects on PMN.
Main Methods:
- Assessing PMN chemiluminescence, superoxide production, and myeloperoxidase (MPO) release.
- Utilizing tumor necrosis factor-alpha (TNF alpha)-primed PMN stimulated with formyl-met-leu-phe (fMLP).
- Investigating the influence of physiological adenosine concentrations and adenosine deaminase treatment.
Main Results:
- Pentoxifylline inhibited TNF alpha-primed PMN chemiluminescence, superoxide production, and MPO release.
- Caffeine stimulated PMN chemiluminescence and MPO release, with no effect on superoxide production.
- Both methylxanthine effects were dependent on adenosine and abolished by adenosine deaminase, independent of cAMP levels.
Conclusions:
- Pentoxifylline decreases PMN activity by enhancing adenosine's inhibitory effects on degranulation and superoxide production.
- Caffeine increases PMN activity by counteracting adenosine's inhibitory effects on degranulation.
- The distinct actions of caffeine and pentoxifylline on PMN activity are adenosine-mediated and not explained by cAMP changes.