Suppressive Effects of Caffeine on the Immune Response of the Mouse to Sheep Erythrocytes 1

Summary The effects of caffeine on the primary immune response of the mouse to sheep erythrocyte were investigated. The addition of caffeine to cultures of spleen cells from mice 4 days after antigenic stimulation showed depressed antibody production. Caffeine in concentrations of 1.9-47 μM gave dose-dependent suppression ranging from 12-72%. Kinetic studies indicated that caffeine (37 μM) depressed antibody production and cell-associated protein synthesis at approximately the same extent. The synthesis of DNA and RNA was not inhibited under these conditions. Synthesis of DNA-dependent RNA and protein could be inhibited by the addition of actinomycin D and puromycin, respectively, to the culture media. When tested in vivo caffeine at a dose of 200 mg/kg body weight given either before or after antigenic stimulation depressed serum antibody levels. The results suggest that caffeine exerts its immunosuppressive effects by depressing protein synthesis, possibly by inhibiting enzymes involved with protein production. The authors wish to thank Drs. John Sugg and Peter Ludovici for helpful suggestions in preparing the manuscript.