EFFECT OF XANTHINE DERIVATIVES ON CHEMOTACTIC POLYPEPTIDE-INDUCED SUPEROXIDE AND ENZYME-RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES

1. We investigated the effects of new xanthine derivatives, 1-methyl-3 -propyl xanthine (MPX) and 1,3-dipropyl xanthine (DPX), and several ot her xanthine derivatives on N-formyl-methionyl-leucyl-phenylalanine-in duced superoxide and lysozyme release from human polymorphonuclear leu cocytes (PMN). 2. MPX and DPX at low concentrations (10(-8)-10(-9) mol /L) inhibited superoxide release from PMN by a maximum of 31.2 +/- 10. 6% and 49.8 +/- 10.4% (mean +/- s.d.), respectively, and 10(-3) mol/L concentrations completely inhibited the release reactions (4.8 +/- 1.2 and 7.6 +/- 2.5% of control level). At 10(-5) mol/ L, however, the in hibition did not occur (99.9 +/- 7.3 and 110.2 +/- 15.8% of control le vel). When PMN was pre-incubated with adenosine deaminase (ADA, 0.1 U/ mL), superoxide release from PMN was inhibited in a dose-dependent man ner by MPX and DPX and the interruption of the inhibition at 10(-5) mo l/ L was not observed. 3. Lysozyme release from PMN was inhibited by M PX at low concentrations (10(-7)-10(-6) mol/L) and high concentrations (10(-3) mol/L). However 10(-4) mol/L of MPX facilitated the release ( 23.7 +/- 27.0%). When pretreated with ADA (0.1 U/mL), MPX suppressed l ysozyme release in a dose-dependent manner and the facilitation of the release at 10(-4) mol/ L was not observed. 4. When comparing effects of some other xanthine derivatives on superoxide release, the interrup tion of the inhibition of superoxide release at 10(-5) mol/ L was comm only observed among xanthine derivatives with adenosine A2 antagonism. 5. The results suggest that adenosine A2 antagonism of xanthine deriv atives may interfere with their anti-inflammatory effects at therapeut ic concentrations (10(-5)-10(-4) mol/ L).