ERYTHROMYCIN INHIBITS TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 PRODUCTION INDUCED BY HEAT-KILLED STREPTOCOCCUS-PNEUMONIAE IN WHOLE-BLOOD

To determine the effects of penicillin and erythromycin on cytokine pr oduction induced by heat-killed Streptococcus pneumoniae (HKSP), we st udied the effects of those drugs on cytokine production induced by S. pneumoniae in human whole blood in vitro and ex vivo. In whole blood i n vitro, erythromycin, but not penicillin, caused a dose-dependent dec rease in HKSP-induced production of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6), while the production of IL-10, IL-12, and ga mma interferon was inhibited only at the highest erythromycin concentr ation tested (10(-3) M). The production of TNF and IL-6 in whole blood obtained from healthy subjects after a 30-min infusion of erythromyci n (1,000 mg) was lower after ex vivo stimulation with HKSP than that i n blood drawn before the infusion. Inhibition of TNF contributed to er ythromycin-induced inhibition of IL-6 synthesis. Inhibition of TNF and IL-6 production by erythromycin may have a negative impact on host de fense mechanisms during pneumococcal pneumonia.