Beta-lactam antibiotics and human lymphocyte function: the in vitro effect on blastogenesis, lymphokine production...

The effects of penicillin, cephalothin and cefoxitin on lymphokine production and mitogen stimulation of human peripheral blood lymphocytes and suppressor cell functions in man were studied with concentrations achievable in serum. Penicillin (50 and 100 micrograms/ml) and cephalosporins (50 and 100 micrograms/ml) directly stimulated production of the lymphokine leukocyte aggregating factor (LAgF) by unstimulated lymphocytes and enhanced mitogen-stimulated production of this lymphokine. Neither beta-lactam derivative interfered directly with neutrophil aggregation. Using the same concentration, penicillin did not suppress but had either no effect on or slightly increased the unstimulated and mitogen-stimulated lymphocyte transformation responses, whereas cephalosporins significantly suppressed both responses. Suppression of blastogenesis by the latter could be mediated through suppressor cell enhancement as indicated by the significant suppressed lymphocyte transformation observed while using the supernatant of cephalosporin-stimulated and cultured lymphocytes. This suppressive activity was more pronounced with cephalothin than with cefoxitin while it was not observed with penicillin which rather stimulated thymidine uptake. These findings suggest that enhancement of lymphokine production and suppression of lymphocyte transformation by cephalosporins are not contradictory and reflect a stimulating effect on two different lymphocyte subsets. The enhancement of suppressor function might account for the lower incidence of late hypersensitivity reactions observed in patients treated with the cephalosporins compared with those treated with penicillins.