title: Macrolide antibiotics aggravate experimental autoimmune encephalomyelitis and inhibit inducible nitric oxide synthase.
abstract: Recent studies have implicated Chlamydia pneumoniae (C. pneumoniae) is present in a subset of patients with multiple sclerosis (MS) in which C. pneumoniae could act as a cofactor in the development of the disease. Macrolide antibiotics are most widely used anti-chlamydial agents and have immunomodulatory effect independently of their anti-bacterial activity. To investigate their effects on experimental autoimmune encephalomyelitis (EAE), EAE was induced by immunization with MBP68-86 peptide emulsified in complete Freund's adjuvant (CFA). Clarithromycin (CM) or azithromycin (AM, 50 mg/100 g body weight) was administrated daily from day 2 before immunization. All rats developed and survived EAE, but the groups administrated CM or AM had more severe symptoms. On day 11 post-immunization, mononuclear cells (MNCs) were prepared from the spleen of control group and cultured with or without macrolide antibiotics (10mug/ml). We evaluated nitric oxide (NO) production in the serum and culture supernatant. Inducible nitric oxide synthase (iNOS) mRNA and protein expression in the spinal cords and cultured MNCs were measured. The results showed that CM and AM similarly inhibited NO production and iNOS mRNA and protein expression in vivo and in vitro. Macrolide antibiotics may aggravate EAE by inhibiting iNOS mRNA and protein expression. Further studies are needed to investigate the effect of macrolide antibiotics on MS and to compare the effect of different anti-chlamydial antibiotics on MS.
authors.affiliation: Department of Neurology, The Third Affiliated hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Dunjing
authors.initials: D
authors.lastname: Wang
authors.forename: Zhengqi
authors.initials: Z
authors.lastname: Lu
authors.forename: Liping
authors.initials: L
authors.lastname: Hu
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Hu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D017963:Azithromycin / Q000276:immunology / Q000633:toxicity*; D015153:Blotting, Western; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000188:drug therapy / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000187:drug effects; D017291:Clarithromycin / Q000633:toxicity*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000276:immunology / Q000382:microbiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018942:Macrolides / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D009842:Oligopeptides; D009569:Nitric Oxide; D017963:Azithromycin; D052247:Nitric Oxide Synthase Type II; D017291:Clarithromycin