Nadifloxacin, an antiacne quinolone antimicrobial, inhibits the production of proinflammatory cytokines by human peripheral blood mononuclear cells and normal human keratinocytes.
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.
Kuwahara
Keiichi
K
Ako Research Institute, Otsuka Pharmaceutical Co. Ltd., 1122-73 Nishihamakita-cho, Ako, Hyogo 678-0207, Japan.
Kitazawa
Toshiki
T
Kitagaki
Hideki
H
Tsukamoto
Teruhisa
T
Kikuchi
Mikio
M
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
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