Summary
The effect of 20 different antibiotics on the incorporation of3H-thymidine by human peripheral T-lymphocytes in serum-free medium stimulated by PHA was studied. Of the antibiotics tested fusidic acid and rifampin had a pronounced inhibiting effect at therapeutic concentrations. At concentrations above the therapeutic level a marked inhibiting effect was detected for tetracyclines, erythromycin, clindamycin and nitrofurantoin. No apparent inhibiting effect on the PHA-response of human lymphocytes could be detected for penicillins, cephalosporins, sulfametoxazol, aminoglycoside-antibiotics, nalidixic acid, chloramphenicol and fluorocytosin. In another group of experiments we studied the incorporation of thymidine by human peripheral B lymphocytes in the presence of antibiotics. KilledStaphylococcus aureus Cowan I was used as a selective B-lymphocyte mitogen. The Cowan I stimulation was inhibited by fusidic acid and rifampin at therapeutic concentrations and by erythromycin, clindamycin and nitrofurantoin at concentrations above the therapeutic level. In a third group of experiments the incorporation of14C-leucine by non-stimulated human peripheral lymphocytes was studied in the presence of fusidic acid. In this type of experiment an inhibitory effect at therapeutic concentrations was also detected. It is suggested that some antibiotics acting by protein synthesis inhibition also affect the protein synthesis and function of human lymphocytes during the phase of inhibition. However, the influence of albumin binding on the immunodepression by the different antibiotics is not known. The albumin binding for fusidic acid is high and this may reduce the in vivo effect of this drug. Thus, whether these impairments of lymphocyte function also take place in vivo remains unknown.
Zusammenfassung
Es wurde die Wirkung von 20 verschiedenen Antibiotika auf den Einbau von3H-Thymidin durch menschliche Lymphozyten des strömenden Blutes nach Stimulierung durch Phythämagglutinin (PHA) untersucht. Unter den geprüften Antibiotika hatten Fusidinsäure und Rifampicin in therapeutischen Konzentrationen eine ausgeprägte Hemmwirkung. In darüberliegenden Konzentrationen bestand eine deutliche Hemmwirkung durch Tetracycline, Erythromycin, Clindamycin und Nitrofurantoin. Kein Hemmeffekt auf die PHA-Reaktion menschlicher Lymphozyten war nachzuweisen für Penicilline, Cephalosporine, Sulfamethoxazol, Aminoglykoside, Nalidixinsäure, Chloramphenicol und Fluorocytosin. In einer anderen Versuchsreihe untersuchten wir den Thymidineinbau durch menschliche B-Lymphozyten des strömenden Blutes nach Stimulierung mitStaphylococcus aureus Cowan I in Gegenwart von Antibiotika, die die PHA-Reaktion hemmten. Die Stimulierung durch Cowan I wurde gehemmt durch Fusidinsäure und Rifampicin in therapeutischen Konzentrationen und durch Erythromycin, Clindamycin und Nitrofurantoin in übertherapeutischen Konzentrationen. In einer dritten Versuchsgruppe wurde der Einbau von14C-Leuzin durch nichtstimulierte menschliche Lymphozyten des strömenden Blutes in Gegenwart von Fusidinsäure untersucht. Auch hier wurde eine Hemmwirkung therapeutischer Konzentrationen nachgewiesen. Es wird angenommen, daß manche, durch Proteinsynthesehemmung wirkende Antibiotika auch die Proteinsynthese und Funktion menschlicher Lymphozyten beeinträchtigen.
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Forsgren, A., Banck, G. Influence of antibiotics on lymphocyte function in vitro. Infection 6 (Suppl 1), S91–S97 (1978). https://doi.org/10.1007/BF01646075
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DOI: https://doi.org/10.1007/BF01646075