title: In Vitro Anti-inflammatory and Immunomodulatory Effects of Ciprofloxacin or Azithromycin in Staphylococcus aureus-Stimulated Murine Macrophages are Beneficial in the Presence of Cytochalasin D.
abstract: We hypothesized that if internalization of Staphylococcus aureus could be blocked by using cytochalasin D (an inhibitor of phagocytosis and phagolysosome fusion), then the intracellular entry and survival of the pathogen in host's phagocytic cells recruited to the inflammatory site can be restricted. At the same time, if we use antimicrobial agents (e.g., ciprofloxacin and azithromycin) having potent intracellular and extracellular microbicidal activity against the bacterium that have not entered into the phagosome and remains adhered to the phagocytic cell membrane, then they can be eradicated from the site of infection without compromising the host cell. To validate this, role of ciprofloxacin (CIP) and azithromycin (AZM) in eliminating S. aureus by suppressing the phagocytic activity of macrophages with cytochalasin D before infection was investigated. CIP and AZM were used either alone or in combination with cytochalasin D. Supernatant and lysate obtained from the culture of macrophages were used for quantification of reactive oxygen species, lysozymes, antioxidant enzymes, and cytokines produced. Azithromycin was better than ciprofloxacin in combination with cytochalasin D for eradicating S. aureus and regulating cytokine release. Further studies are required for ensuring proper delivery of this combination at the site of infection.
authors.affiliation: Department of Physiology, Immunology Laboratory, University Colleges of Science and Technology, University of Calcutta, 92 APC Road, Calcutta, 700009, West Bengal, India.
authors.forename: Somrita
authors.initials: S
authors.lastname: Dey
authors.forename: Arnab
authors.initials: A
authors.lastname: Majhi
authors.forename: Sayantika
authors.initials: S
authors.lastname: Mahanti
authors.forename: Ipsita
authors.initials: I
authors.lastname: Dey
authors.forename: Biswadev
authors.initials: B
authors.lastname: Bishayi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D017963:Azithromycin / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D015638:Cytochalasin D / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009113:Muramidase / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C556062:IL10 protein, mouse; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015638:Cytochalasin D; D002939:Ciprofloxacin; D007371:Interferon-gamma; D017963:Azithromycin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D009113:Muramidase; D005978:Glutathione