Effects of moxifloxacin in zymogen A or S. aureus stimulated human THP-1 monocytes on the inflammatory process and the spread of infection.
Antimicrobial agents have been reported to exhibit immunomodulatory and anti-inflammatory activities, both in vivo and in vitro (e.g., in human lymphocytes, macrophages and monocytes). The effects of moxifloxacin on cytokine immunomodulatory mediators, free radical generation and hydrolytic enzyme activities in zymogen A-stimulated human THP-1 monocytes were evaluated. An increase in c-AMP levels, protein kinase C activity, and the release of nitric oxide and hydrogen peroxide with a decrease in pH occurred within the first hour. Further, the effects of moxifloxacin were reduced by agents which blocked the oxygen burst, lysosome-phagosome fusion, and the energy generation within the cell. After 4 h, there was a decrease in NAG and cathepsin D activities, lipid peroxidation and the release of pro-inflammatory cytokines. These data indicate that moxifloxacin may modify the acute-phase inflammatory responses through inhibition of cytokine release in monocytes. Moxifloxacin inhibited the release of TNFalpha, IL-1, IL-6, and IL-8 in a concentration-dependent manner across a range of 0.004 to 4 microg/mL. After 4 h, there was a decrease in the release of these cytokines, thus interfering with the inflammation process to reduce infection and its spread. The effects of moxifloxacin appear initially to activate monocytes to kill bacteria through the innate immune process by releasing ROS and lysosomal hydrolytic enzymes as well as phagocytosis of the organism. At a later time the bacteria are killed through a Bacterialstatic mechanism of protein synthesis inhibition and there is a reversal of the effects of moxifloxacin on cytokine release, free radical generation and hydrolytic enzymes so that lipid peroxidation and tissue destruction by the infection process is suppressed.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001372:Aza Compounds; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000494:pharmacology*; D024841:Fluoroquinolones; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000077266:Moxifloxacin; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011804:Quinolines; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000890:Anti-Infective Agents; D001372:Aza Compounds; D016207:Cytokines; D004792:Enzyme Precursors; D024841:Fluoroquinolones; D011804:Quinolines; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D011493:Protein Kinase C; D000077266:Moxifloxacin