ORIGINAL ARTICLE Linezolid Diminishes Inflammatory Cytokine Production from Human Peripheral Blood Mononuclear Cells Pilar Garcia-Roca, a Javier Mancilla-Ramirez, b Araceli Santos-Segura, a Marisol Ferna ´ndez-Avile ´s, a and Ernesto Calderon-Jaimes a a Departamento de Inmunoquı ´mica y Biologı ´a Celular, Hospital Infantil de Me ´xico, Federico Go ´mez, Me ´xico, D.F., Me ´xico b Departamento de Infectologı ´a e Inmunologı ´a Perinatal, Instituto Nacional de Perinatologı ´a, and Escuela Superior de Medicina, Instituto Polite ´cnico Nacional, Me ´xico, D.F., Me ´xico Received for publication January 20, 2005; accepted May 26, 2005 (ARCMED-D-05-00031). Background. Active peptides produced by monocytes, in response to endotoxin, initiate and maintain the acute phase of inflammatory response. Some antibiotics have been reported to have immunomodulatory effects in addition to their antimicrobial activity. We examined the effect of linezolid on cytokine synthesis. Methods. The modulatory effects of erythromycin and linezolid were evaluated in LPS- stimulated human peripheral blood mononuclear cells (PBMCs). Blood was obtained by venipuncture from healthy donor volunteers. PBMCs were separated by Ficoll-Paque. More than 90% of the cells were monocytes as determined by esterase staining. Cells were incubated in the presence of LPS, with or without various concentrations of eryth- romycin and linezolid. The concentration of each cytokine was determined by ELISA with commercially available reagents. Results. The two drugs suppressed significantly the synthesis of the cytokines tested in a concentration-dependent manner. Conclusions. These data indicate that antibacterial agents may modify acute phase in- flammatory response through their effects on cytokines synthesis by monocytes. Ó 2006 IMSS. Published by Elsevier Inc. Key Words: Production of cytokines, Modulatory effects of antibiotics, Effect of antibiotics on cytokine production. Introduction Antibiotics are widely used as bacteriostatic or bactericidal drugs for therapy for bacterial infections. Besides the re- spective interactions between antibiotics and bacteria and between the immune system and bacteria, several antibiot- ics are bifunctional drugs because they have an anti-inflam- matory effect in addition to their microbicidal effect (1–3). The immunomodulatory effects of antibiotics include al- teration of phagocytosis, chemotaxis, endotoxin release, NADPH oxidase activity, modulation of production of var- ious cytokines such as interleukin-1 (IL-1), IL-2, IL-6, IL-8, tumor necrosis factor alpha (TNF-a) and many other miscellaneous activities (3–5). Cytokines are essential mediators of cell-to-cell signals in physiological and pathological immune responses and in the inflammatory response. Under normal conditions, these cytokines act as crucial signals in the development of appropriate defenses; however, exaggerated or prolonged release can lead to pathological conditions. Several studies have indicated that the excessive production of host inflam- matory cytokines might be responsible for the mortality associated with septic shock (6,7). Sepsis and septic shock are life-threatening conditions characterized by fever (sometimes hypothermia), organ fail- ure, and low blood pressure. Despite recent advances in anti- microbial therapy, the mortality rate due to sepsis caused by gram-negative bacteria remains high at present (8). Address reprint requests to: E. Caldero ´n, Departamento de Inmunoquı ´- mica y Biologı ´a Celular, Edif. Mundet, 3er piso, Hospital Infantil de Me ´x- ico Federico Go ´mez, Dr. Ma ´rquez 162, Col. Doctores, 06720 Me ´xico, D.F., Me ´xico; E-mail: ecalderj@yahoo.com 0188-4409/06 $–see front matter. Copyright Ó 2006 IMSS. Published by Elsevier Inc. doi: 10.1016/j.arcmed.2005.05.022 Archives of Medical Research 37 (2006) 31–35