title: Nadifloxacin, an antiacne quinolone antimicrobial, inhibits the production of proinflammatory cytokines by human peripheral blood mononuclear cells and normal human keratinocytes.
abstract: BACKGROUND
  Acne vulgaris is a chronic inflammatory disease involving colonization of Propionibacterium acnes (P. acnes), activation of neutrophils and lymphocytes. Circumstantial evidence suggests that antigen-independent and -dependent immune responses against P. acnes are involved in the pathogenesis of inflammatory acne. Epidermal keratinocytes are also suggested to be involved in initiation and progression of cutaneous inflammation. Nadifloxacin, a fluorinated quinolone, has potent antimicrobial activities against Gram-negative and -positive microbes and is used to treat multiple inflamed acne lesions. However, its effect on immune conferring cells such as mononuclear cells and keratinocytes has not been examined.
  
  
  OBJECTIVE
  To evaluate the possible involvement of potential anti-inflammatory activity of nadifloxacin in its therapeutic effect on inflammatory acne, we examined the effects of nadifloxacin, in comparison with other antibiotics used to treat acne vulgaris, on cytokine production by human peripheral blood mononuclear cells (PBMC) and keratinocytes.
  
  
  METHODS
  Cytokine production by PBMC was determined after treatment with heat-killed P. acnes in the presence or absence of antimicrobials using a real-time PCR and ELISA. Cultured human epidermal keratinocytes were stimulated by IFN-gamma plus IL-1beta and the effects of antimicrobials were examined by using ELISA.
  
  
  RESULTS
  Nadifloxacin as well as macrolide antibiotics and clindamycin inhibited IL-12 and IFN-gamma production by PBMC stimulated by heat-killed P. acnes. The drug also inhibited the IL-1alpha, Il-6, IL-8 and GM-CMS production by keratinocytes treated with IFN-gamma plus IL-1beta.
  
  
  CONCLUSIONS
  Inhibitory effects of nadifloxacin to activate T cells and keratinocytes may be involved at least in part in the mechanism of its therapeutic effect against inflammatory acne.
authors.affiliation: Ako Research Institute, Otsuka Pharmaceutical Co. Ltd., 1122-73 Nishihamakita-cho, Ako, Hyogo 678-0207, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kuwahara
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kitazawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Kitagaki
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Mikio
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy; D000287:Administration, Topical; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002981:Clindamycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D003352:Corynebacterium / Q000502:physiology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003879:Dermatologic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011425:Propionibacterium acnes / Q000502:physiology; D011807:Quinolizines / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D003879:Dermatologic Agents; D004338:Drug Combinations; D024841:Fluoroquinolones; D018836:Inflammation Mediators; D007375:Interleukin-1; D011807:Quinolizines; D002981:Clindamycin; C062127:nadifloxacin; D007371:Interferon-gamma