title: Erythromycin inhibits tumor necrosis factor alpha and interleukin 6 production induced by heat-killed Streptococcus pneumoniae in whole blood.
abstract: To determine the effects of penicillin and erythromycin on cytokine production induced by heat-killed Streptococcus pneumoniae (HKSP), we studied the effects of those drugs on cytokine production induced by S. pneumoniae in human whole blood in vitro and ex vivo. In whole blood in vitro, erythromycin, but not penicillin, caused a dose-dependent decrease in HKSP-induced production of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6), while the production of IL-10, IL-12, and gamma interferon was inhibited only at the highest erythromycin concentration tested (10(-3) M). The production of TNF and IL-6 in whole blood obtained from healthy subjects after a 30-min infusion of erythromycin (1,000 mg) was lower after ex vivo stimulation with HKSP than that in blood drawn before the infusion. Inhibition of TNF contributed to erythromycin-induced inhibition of IL-6 synthesis. Inhibition of TNF and IL-6 production by erythromycin may have a negative impact on host defense mechanisms during pneumococcal pneumonia.
authors.affiliation: Department of Infectious Diseases, Tropical Medicine and AIDS, University of Amsterdam, The Netherlands. m.j.schultz@amc.uva.nl
authors.forename: M J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: P
authors.initials: P
authors.lastname: Speelman
authors.forename: S
authors.initials: S
authors.lastname: Zaat
authors.forename: S J
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D010406:Penicillins / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D015850:Interleukin-6; D010406:Penicillins; D014409:Tumor Necrosis Factor-alpha; D004917:Erythromycin