title: Dakin solution alters macrophage viability and function.
abstract: BACKGROUND
  Macrophages are important in wound defense and healing. Dakin's solution (DS), buffered sodium hypochlorite, has been used since World War I as a topical antimicrobial for wound care. DS has been shown to be toxic to host cells, but effects on immune cells are not well documented.
  
  
  METHODS
  DS at 0.5%, 0.125%, and ten-fold serial dilutions from 0.25%-0.00025% were evaluated for cellular toxicity on murine macrophages (J774A.1). The effect of DS on macrophage adhesion, phagocytosis, and generation of reactive oxygen species was examined. Macrophage polarization following DS exposure was determined by gene expression using quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  Concentrations of DS >0.0025% reduced macrophage viability to <5% in exposure times as short as 30 s. Similarly, phagocytosis of Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus flavus were significantly reduced at all tested concentrations by macrophages pretreated with DS. H2O2 production was reduced by 8%-38% following treatment with 0.00025%-0.125% DS. Macrophage adherence was significantly increased with >0.0025% DS after 15 min of exposure compared with controls. Quantitative real-time polymerase chain reaction demonstrated that DS exposure resulted in classical macrophage activation, with increased expression of inducible nitric oxide synthase 2, interferon-γ, and interleukin (IL)-1β.
  
  
  CONCLUSIONS
  DS at clinically used concentrations (0.025%-0.25%) was detrimental to macrophage survival and function. For optimal clinical use, understanding the impact of DS on macrophages is important as depletion may result in impaired pathogen clearance and delayed healing. These findings indicate that 0.00025% DS is a safe starting dose; however, optimal use of DS requires further validation with in vivo models.
authors.affiliation: Infectious Disease Service, MCHE-MDI, Brooke Army Medical Center, JBSA Fort Sam Houston, Texas. Electronic address: anthony.p.cardile.mil@mail.mil.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Cardile
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Sanchez
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Sharanda K
authors.initials: SK
authors.lastname: Hardy
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Desiree R
authors.initials: DR
authors.lastname: Romano
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Brady J
authors.initials: BJ
authors.lastname: Hurtgen
authors.affiliation: Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
authors.affiliation: Infectious Disease Service, MCHE-MDI, Brooke Army Medical Center, JBSA Fort Sam Houston, Texas.
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
authors.affiliation: Infectious Disease Service, MCHE-MDI, Brooke Army Medical Center, JBSA Fort Sam Houston, Texas; Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Akers
mesh_terms: D000328:Adult; D000818:Animals; D001228:Aspergillosis / Q000188:drug therapy / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D004202:Disinfectants / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology; D012973:Sodium Hypochlorite / Q000494:pharmacology*; D012996:Solutions / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology; D013530:Surgical Wound Infection / Q000188:drug therapy* / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: D004202:Disinfectants; D012996:Solutions; D012973:Sodium Hypochlorite
keywords: Dakin solution; Macrophages; Phagocytosis; Sodium hypochlorite