JAC ADVANCE ACCESS ORIGINALLY PUBLISHED ONLINE ON JANUARY 29, 2008 Journal of Antimicrobial Chemotherapy 2008 61(3):554-560; doi:10.Article All Versions of this Article: 61/3/554 _most recent_ Services Google Scholar PubMed ORIGINAL RESEARCH AZITHROMYCIN ALTERS MACROPHAGE PHENOTYPE BRIAN S.VIDYA SUNDARESHAN1, THEODORE J.DON HAYES, JR1,3, MICHAEL I.AND DAVID J._ 1 Department of Internal Medicine, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA 2 Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 725 Rose Street, Lexington, KY 40536, USA 3 Department of Pediatrics, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA _ _Received 24 August 2007;_ _returned 14 November 2007;_ _revised 2 October 2007;_ _accepted 28 December 2007_ Corresponding author.+1-859-323-8751; Fax: +1-859-323-0069; E-mail: djfeol2{at}email.Objectives: To investigate the _in vitro_ effects of azithromycin on macrophage phenotype.A mouse macrophage cell line (J774), we examined the effect of azithromycin on the properties that define classical macrophage activation (M1) and alternative macrophage activation (M2).J774 cells were cultured in the presence of azithromycin and stimulated with classical activation cytokines along with lipopolysaccharide (LPS).Were analysed for inflammatory cytokine production, surface receptor expression, inducible nitric oxide synthase (iNOS) protein expression and arginase activity.Azithromycin altered the overall macrophage phenotype.Demonstrated a significantly reduced production of the pro-inflammatory cytokines IL-12 and IL-6, increased production of the anti-inflammatory cytokine IL-10 and decreased the ratio of IL-12 to IL-10 by 60%.Expression indicative of the M2 phenotype (mannose receptor and CD23) was increased, and receptor expression typically up-regulated in M1 cells (CCR7) was inhibited.Presence of azithromycin increased arginase (M2 effector molecule) activity 10-fold in cells stimulated with IFN and LPS, and iNOS protein (M1 effector molecule) concentrations were attenuated by the drug.These data provide evidence that azithromycin affects the inflammatory process at the level of the macrophage and shifts macrophage polarization towards the alternatively activated phenotype.Defined M2 phenotype has been described in conditions in which pulmonary inflammation and fibrosis are major determinants of clinical oue, but the concept of antibiotics altering macrophage phenotype has not yet been critically evaluated.Read more Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration
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