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 delayed initiation of antibody formation during the primary response. However, OTC exposure had no effect on either the peak time of antibody response 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 concanavalin was equivocal. However, allogeneic stimulation of MSL was inhibited at 100 micrograms/ml OTC. There was also a decrease in the number of cells recovered. OTC had no effect on lymphocyte cytotoxicity in cells cultured in vitro. OTC inhibited the cytotoxic response of Corynebacterium parvum-elicited PEM at 10 micrograms/ml (effector:target of 10:1). Low levels of OTC (1-10 micrograms/ml) augmented the cytotoxic response (effector:target of 5:1). The effect of OTC on induction of PEM cytotoxicity was assessed by coculturing thioglycollate-elicited (TG) PEM in vitro with IFN-gamma and endotoxin along with 0-100 micrograms/ml OTC. Induction of cytotoxicity was inhibited at 0.5 microgram/ml. The effect of OTC on TG-PEM antimicrobial activity was assessed by measuring reduction of nitroblue tetrazolium (NBT) and cytochrome C. OTC inhibited the reduction of NBT at 500 micrograms/ml following PMA stimulation of TG-PEM. OTC had no effect on either NBT or cytochrome C reduction following stimulation with opsonized zymosan. These results demonstrate that OTC-mediated immunosuppression is a multifaceted event, with differing sensitivities both between immune cells and between different pathways within the same cell.
Myers
M J
MJ
Animal Biology Branch, US FDA, Beltsville, MD 20705, USA.
Farrell
D E
DE
Henderson
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D007121:Immunocompetence / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010118:Oxytetracycline / Q000494:pharmacology*; D011425:Propionibacterium acnes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D000276:Adjuvants, Immunologic; D014409:Tumor Necrosis Factor-alpha; D010118:Oxytetracycline