OXYTETRACYCLINE-MEDIATED ALTERATION OF MURINE IMMUNOCOMPETENCE

The immunomodulatory effect of oxytetracycline (OTC) on murine splenic lymphocytes (MSL), peritoneal exudate macrophage (PEM) functions and antibody production was examined. In vivo exposure to OTC slightly del ayed initiation of antibody formation during the primary response. How ever, OTC exposure had no effect on either the peak time of antibody r esponse or peak antibody titer. OTC also had no significant effect on the secondary antibody response. Mitogen-induced proliferation of MSL cocultured with OTC and pokeweed mitogen, phytohemagglutinin or concan avalin was equivocal. However, allogeneic stimulation of MSL was inhib ited at 100 mu g/ml OTC. There was also a decrease in the number of ce lls recovered. OTC had no effect on lymphocyte cytotoxicity in cells c ultured in vitro. OTC inhibited the cytotoxic response of Corynebacter ium parvum-elicited PEM at 10 mu g/ml (effector:target of 10:1). Low l evels of OTC (1-10 mu g/ml) augmented the cytotoxic response (effector :target of 5:1). The effect of OTC on induction of PEM cytotoxicity wa s assessed by coculturing thioglycollate-elicited (TG) PEM in vitro wi th IFN-gamma and endotoxin along with 0-100 mu g/ml OTC. Induction of cytotoxicity was inhibited at 0.5 mu g/ml. The effect of OTC on TG-PEM antimicrobial activity was assessed by measuring reduction of nitrobl ue tetrazolium (NET) and cytochrome C. OTC inhibited the reduction of NET at 500 mu g/ml following PMA stimulation of TG-PEM. OTC had no eff ect on either NET or cytochrome C reduction following stimulation with opsonized zymosan. These results demonstrate that OTC-mediated immuno suppression is a multifaceted event, with differing sensitivities both between immune cells and between different pathways within the same c ell.