Inhibitory effect of anaphylactic shock by caffeine in rats

Caffeine is known to reduce evoked histamine secretion, but the effects of caffeine on anaphylactic shock have not been clarified. We have investigate d the effects of caffeine on anaphylactic shock in rats. Systemic anaphylac tic shock by compound 48/80 injection was monitored for 1 h. An IgE-depende nt local anaphylactic shock was generated by sensitizing the skin with anti -dinitrophenyl (DNP) IgE followed 48 h later with an injection of antigen. Caffeine inhibited compound 48/80-induced anaphylatic shock to 40% with a d ose of 1 mg/kg. Caffeine (0.1 mg/kg) inhibited to 56.4 +/- 0.4% passive cut aneous anaphylactic shock activated by anti-DNP IgE. Caffeine (5-20 mM) sig nificantly inhibited histamine release from rat peritoneal mast cells (RPMC s) activated by compound 48/80 or anti-DNP IgE, Especially, caffeine (20 mM ) inhibited by 96.7 +/- 0.5% histamine release activated by compound 48/ 80 , Moreover, caffeine (1-20 mM) had a significant inhibitory effect on anti- DNP IgE-induced tumor necrosis factor-ct production from RPMCs. The level o f cAMP in RPMCs, when caffeine (20 mM) was added, increased significantly a fter 5-60 min compared with that of a normal control. These results indicat e that caffeine inhibits immediate-type allergic reactions by inhibition of mast cell degranulation in vivo and in vitro. (C) 2000 International Socie ty for Immunopharmacology. Published by Elsevier Science Ltd. All rights re served.