title: The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study.
abstract: BACKGROUND
  The role of myeloperoxidase (MPO) is essential in the killing of phagocytosed bacteria. Certain steroid hormones increase MPO plasma concentration. Our aim was to test the effect of MPO, its inhibitor indomethacin, and certain steroid hormones on bactericidal activity.
  
  
  METHODS
  Human polymorphonuclear leukocytes (PMN) were incubated with opsonised Escherichia coli and either MPO, indomethacin, estradiol, or hydrocortisone. Intracellular killing capacity was evaluated with UV microscopy after treatment with fluorescent dye. Next, an in vivo experiment was performed with nine groups of rats: in the first phase of the study indomethacin treatment and Pasteurella multocida infection (Ii), indomethacin treatment without infection (I0), untreated control with infection (Mi) and untreated control without infection (M0); in the second phase of the study rats with infection and testosterone treatment (NT), castration, infection and testosterone treatment (CT), castration, infection and estradiol treatment (CE), non-castrated infected control (N0), and castrated infected control (C0). After treatment bacteria were reisolated from the liver and heart blood on agar plates, and laboratory parameters were analyzed. For the comparison of laboratory results ANOVA or Kruskal-Wallis test and LSD post hoc test was used.
  
  
  RESULTS
  Indomethacin did not have a remarkable effect on the bacterial killing of PMNs, while the other compounds increased bacterial killing to various degrees. In the animal model indomethacin and infection caused a poor clinical state, a great number of reisolated bacteria, elevated white blood cell (WBC) count, decreased C-reactive protein (CRP) and serum albumin levels. Testosterone treatment resulted in less bacterial colony numbers in group NT, but not in group CT compared to respective controls (N0, C0). Estradiol treatment (CE) decreased colony numbers compared to control (C0). Hormone administration resulted in lower WBC counts, and in group CE, a decreased CRP.
  
  
  CONCLUSIONS
  MPO, estradiol, and hydrocortisone improve bacterial killing activity of PMNs. Indomethacin treatment and castration weaken immune responses and clinical state of infected rats, while testosterone and estradiol have a beneficial effect.
authors.forename: Júlia
authors.initials: J
authors.lastname: Stark
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.forename: Ágoston
authors.initials: Á
authors.lastname: Ghidán
authors.forename: Péter
authors.initials: P
authors.lastname: Vajdovich
authors.forename: Dezső
authors.initials: D
authors.lastname: Szombath
authors.forename: István
authors.initials: I
authors.lastname: Marczell
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Várbíró
authors.forename: Elek
authors.initials: E
authors.lastname: Dinya
authors.forename: Tibor
authors.initials: T
authors.lastname: Magyar
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Béla
authors.initials: B
authors.lastname: Székács
authors.forename: Károly
authors.initials: K
authors.lastname: Nagy
authors.forename: Károly
authors.initials: K
authors.lastname: Rácz
authors.affiliation: Faculty of Medicine, 2nd Department of Internal Medicine, Semmelweis University, 46, Szentkiralyi u,, H-1088 Budapest, Hungary. bekesi.gabor@med.semmelweis-univ.hu.
authors.forename: Gábor
authors.initials: G
authors.lastname: Békési
mesh_terms: D000328:Adult; D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000627:therapeutic use; D001770:Blood Bactericidal Activity; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D050296:Microbial Viability / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D010326:Pasteurella Infections / Q000382:microbiology; D016979:Pasteurella multocida / Q000187:drug effects* / Q000302:isolation & purification; D009195:Peroxidase / Q000378:metabolism* / Q000627:therapeutic use; D017208:Rats, Wistar; D013256:Steroids / Q000378:metabolism* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D013256:Steroids; D009195:Peroxidase; D007213:Indomethacin