title: Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats.
abstract: OBJECTIVE
  Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined.
  
  
  METHODS
  Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation.
  
  
  RESULTS
  Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48+cells) at days 1 and 3 post implantation and CD11b+cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged.
  
  
  CONCLUSIONS
  Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Mirkov
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Popov Aleksandrov
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Demenesku
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Ninkov
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.
authors.forename: Dina
authors.initials: D
authors.lastname: Mileusnic
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.|b Institute of Zoology, Faculty of Biology, University of Belgrade , Belgrade , Serbia , and.
authors.forename: Dragan
authors.initials: D
authors.lastname: Kataranovski
authors.affiliation: a Ecology Department, Institute for Biological Research "Sinisa Stankovic", University of Belgrade , Belgrade , Serbia.|c Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade , Belgrade , Serbia.
authors.forename: Milena
authors.initials: M
authors.lastname: Kataranovski
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011145:Polyvinyls / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D016207:Cytokines; D011145:Polyvinyls; C026699:ivalon sponge; D009569:Nitric Oxide; D014859:Warfarin; D009195:Peroxidase
keywords: Inflammation; T cells; rats; subcutaneous polyvinyl sponge implants; warfarin