Antibiotics and suppression of lymphocyte function in vitro

Abstract

The effects on the mitogenic response of human T lymphocytes were studied for 20 different antibiotics. No apparent inhibitory effect could be detected for penicillins, cephalosporins, aminoglycosides, chloramphenicol, sulfamethoxazole, trimethoprim, nalidixic acid, and 5-fluorocytosine. There were effects at high concentrations with erythromycin, clindamycin, and rifampin, and these antibiotics could also be shown to depress the mitogenic response of B lymphocytes. With fusidic acid, nitrofurantoin, and doxycycline there was an inhibiting effect at low concentrations on the mitogenic responses of B and T lymphocytes and on in vitro antibody production. Protein synthesis in unstimulated lymphocytes was also inhibited. Some antibiotics thus may impair the function of human lymphocytes in vitro.Antibiotics, such as actinomycin D and doxorubicin, are used as immunosuppressive agents, and some antibiotics used in the treatment of bacterial and fungal infections have also been shown to depress granulocyte and lymphocyte functions in vitro (7, 11-13, 15, 19, 20-22, 25-27) and the immune response in humans and experimental animals (2, 3,8,16,21,23).The in vitro effects of a wide range of antibiotics on granulocyte chemotaxis and lymphocyte function were recently reported from our laboratory (11, 12). The aim of the present study was to extend the investigations on the in vitro functions of human B and T lymphocytes in the presence of commonly used antibiotics. MATERIALS AND METHODS Antibiotics

The influence of tetracyclines on T cell activation

“…Moreover, lipid-soluble tetracyclines have been reported to accumulate in leucocytes [9,41,42]. In agreement with the latter are the in vitro sludies that demonstrated that lipidsoluble tetracyclines are more potent inhibitors of mitogenindueed prohferation than non-lipid-soluble ones [13][14][15][16].…”

“…the rejection of transplants [8][9][10][11] and levels of serum immunoglobulin [9,12]. Furthermore, in vitro tetracyclines inhibited the proliferative response of human peripheral blood mononuclear cells (PBMC) to mitogens [13][14][15][16].…”

Quinolones affect thymidine incorporation into the DNA of human lymphocytes

“…In previous studies from our laboratory, we reported the inhibitory effects of various antibiotics on the mitogenic response of human lymphocytes (3,7,9). Some of these antibiotics (e.g., tetracyclines, rifampin, and fusidic acid) have also been shown to impair the immune response in vivo (4-6, 10, 12-14).…”

Some tetracycline drugs suppress mitogen‐stimulated lymphocyte growth but others do not.

“…It is possible that in certain tissues (such as liver) this effect is limited by failure of the drug to penetrate cells (Franklin, 1963), but this is unlikely to be important with human leucocytes since Brown & Percival (1978) have shown that their cell membranes are fairly permeable to these drugs. Banck & Forsgren (1979) have argued that tetracyclines act on mammalian cells by interference with protein synthesis. Potts et al (1983) have recently shown that doxycycine causes an almost insignificant reduction in early RNA synthesis, without interference with volume growth: the rate of recruitment of cells into the first S-phase is reduced and the cells increase in number at a slower rate than normal.…”

“…Certain tetracycline drugs (such as doxycycine and minocycine), but not others (such as tetracycline and oxytetracycline), suppress the growth of mitogenstimulated human lymphocytes when present in the culture fluid at concentrations comparable to peak blood levels sometimes achieved during treatment of infections (Banck & Forsgren, 1979;Thong & Ferranti, 1979). Finch (1980) has argued that it is unlikely that any of the tetracycline drugs will have an appreciable adverse effect on the immune response during the treatment of an acute infection in a previously healthy person since the duration of treatment with the antibiotic is short relative to the timecourse of the immunological reaction, but he has emphasized that the immunosuppressive effects of antimicrobial agents may be clinically relevant in long-term chemotherapy for chronic infections.…”