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Antimicrobial Agents and Chemotherapy, July 1998, p. 1605-1609, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Erythromycin Inhibits Tumor Necrosis Factor Alpha and Interleukin 6 Production Induced by Heat-Killed Streptococcus pneumoniae in Whole Blood

Marc J. Schultz,1,* Peter Speelman,1 Sebastian Zaat,2 Sander J. H. van Deventer,3 and Tom van der Poll1,3

Department of Infectious Diseases, Tropical Medicine and AIDS,1 Department of Medical Microbiology,2 and Laboratory of Experimental Internal Medicine,3 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Received 28 October 1997/Returned for modification 3 March 1998/Accepted 9 April 1998

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.

* Corresponding author. Mailing address: Academic Medical Center, F4-222, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5669111. Fax: 31-20-6977192. E-mail: m.j.schultz{at}amc.uva.nl.

Antimicrobial Agents and Chemotherapy, July 1998, p. 1605-1609, Vol. 42, No. 7
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.