The inhibitory effect of theophylline on cell cycle kinetics of human lymphocytes in vitro.

The effect of theophylline (TF) on proliferation of lymphocytes in phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) freshly stimulated 3-4 days cultures or of 14-days cultured lymphoblasts was studied. Proliferation was estimated by measurement of incorporation of tritiated thymidine (3H-TdR), and by microscopic analysis of cellular divisions progression up to the 4th generation of cells cultured in presence of 5-bromodeoxyuridine (BrdUrd). The strongest inhibition of proliferation was observed when TF was added at the beginning of the cultures. However, when TF was added for the last 20 h of the cultures, a significant decrease in number of the third (M3) and fourth (M4) generation cells was noted and M3/M4 ratio increased from 6.4 up to 19.1. TF inhibited also incorporation of 3H-TdR into cultured lymphoblasts. The obtained data indicate an inhibitory effect of TF both an activation and cell cycle progression of lymphocytes.