Antimicrobial agents and host defence.

Reports from different laboratories on effects of different antibiotics on host defence are often hard to compare because of differences in experimental design. The purpose of this presentation was to describe the effect of many different antibiotics with the same standardized techniques. E. coli and S. aureus pre-exposed to different beta-lactam antibiotics or gentamicin in subinhibitory concentrations were more susceptible to phagocytosis and killing by granulocytes than non-treated bacteria. A markedly depressed chemotaxis was detected when human leucocytes were incubated with fusidic acid and rifampicin in clinically obtainable concentration and well absorbed tetracyclines at high concentrations. The incorporation of 14C-leucine into a trichloracetic-acid insoluble form by human neutrophils was markedly depressed by the same antibiotics. Many other antibiotics did not inhibit granulocyte or lymphocyte functions. At therapeutic concentrations fusidic acid and rifampicin had a pronounced inhibition effect on the incorporation of 3H-thymidine by human T-lymphocytes stimulated by PHA and B-lymphocytes by S. aureus, Cowan I. At concentrations above the therapeutic level, inhibition was detected for doxycycline, erythromycin, clindamycin and nitrofurantoin. Due to high albumin binding for some of the tested antibiotics and other factors involved, experiments were performed to test whether depression also takes place in vivo. The cellular immunity in mice was registered by monitoring the survival of transplanted heart grafts. Rifampicin at human therapeutic dose had a strong inhibiting effect (p less than 0.001) on the rejection of heart grafts. The effect of doxycycline (2.5 mg/kg/day) and fusidic acid (25 mg/kg/day) was slight but significant (p less than 0.02).