title: Effect of azithromycin on natural killer cell function.
abstract: Azithromycin (AZM), a macrolide antibiotic for treating mycoplasma infections, may exhibit anti-inflammatory activity aside from its antimicrobial effect, providing additional therapeutic benefit. Natural killer (NK) cells, a first-line innate immune defense against microbial invasions, paradoxically exert a detrimental effect in protecting mycoplasma infection. Little was known regarding the effect of AZM on NK cells. In the present study, we investigated the ability of azithromycin to influence natural killer (NK) cell function with regard to activation, apoptosis and cytotoxic function. AZM had little effect on NK receptor expression and cytotoxic function of NK-92 cells. However, AZM did show a dose-dependent suppression on IL-15-induced CD69 expression of primary NK cells. AZM inhibited the cytotoxicity against K562 cells of resting and IL-15 activated primary NK cells possibly through down-regulation of perforin expression, especially on CD16(+)CD56(+) NK subsets. AZM exerted a dose-dependent inhibition of IFN-gamma and TNF-alpha production from NK-92 cells, but did not affect the cytokine production of IL-15 activated primary NK cells. Taken together, AZM down-regulates NK cytotoxicity and cytokine production and may provide therapeutic benefits aside from its antimicrobial activity.
authors.affiliation: Division of Asthma, Allergy, and Rheumatology Department of Pediatrics, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan. sjlino@adm.cgmh.org.tw
authors.forename: Syh-Jae
authors.initials: SJ
authors.lastname: Lin
authors.forename: Dah-Chin
authors.initials: DC
authors.lastname: Yan
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Kuo
authors.forename: Hsiu-Shan
authors.initials: HS
authors.lastname: Hsiao
authors.forename: Pei-Yzu
authors.initials: PY
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D017963:Azithromycin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D055607:Receptors, Natural Killer Cell / Q000096:biosynthesis
chemical_list: D055607:Receptors, Natural Killer Cell; D017963:Azithromycin