Effects of alatrofloxacin, the parental prodrug of trovafloxacin, on phagocytic, anti-inflammatory and immunomodulation events of human THP-1 monocytes.
Alatrofloxacin functions similar to other fluoroquinolone antibiotics in that it not only has antibiotic activity to kill invading organisms by interfering with DNA synthesis, it possesses immunosuppressive activity. In the first hour after bacteria have been phagocytosed by THP-1 monocytes, the drug activates a lytic mechanism involving the release of c-AMP, tumor necrosis factor (TNFalpha), interleukin-1 (IL-1), IL-6 and nitric oxide, with elevations in lysosomal hydrolytic enzyme activities. This effect reverses between 2 and 4 h. At this time, all of these inflammatory processes are returned to normal values or below suggesting that alatrofloxacin reduces the spread of infection and destruction of tissue related to inflammation.
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, NC Chapel Hill 27559-7360, USA. iris_hall@unc.edu
Iris H
IH
Hall
Ute E
UE
Schwab
E Stacy
ES
Ward
Timothy J
TJ
Ives
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009287:Naphthyridines / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D011355:Prodrugs / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D024841:Fluoroquinolones; D009287:Naphthyridines; D011355:Prodrugs; C106856:alatrofloxacin; C080163:trovafloxacin; D013482:Superoxide Dismutase