The effect of indomethacin, myeloperoxidase, and certain steroid hormones on bactericidal activity: an ex vivo and in vivo experimental study

Abstract

BackgroundThe 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.MethodsHuman 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.ResultsIndomethacin 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.ConclusionsMPO, 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.

Kinetic Parameter Analysis of Myeloperoxidase in the Presence of Some Cosusbtrates in Saliva of Newborn at Risk of Sepsis

“…The production of HOCl, HOI, and HOSCN by MPO is essential in host defense mechanisms. These productions deploy bactericidal activity on the bacteria ingested in the phagosome [17].…”

Myeloperoxidase G-463A and CYBA C242T genetic variants in gestational diabetes mellitus

“…Decreased SHBG levels have been found to be associated with hyperinsulinemia, hyperandrogenemia, obesity, oxidative stress, insulin resistance, metabolic syndrome, and type 2 diabetes ( 36 , 37 ). Antioxidant steroids, such as estrogen or testosterone, could enhance MPO activity and improve bacterial killing activity of polymorphonuclear leukocytes ( 38 , 39 ). MPO activity in neutrophils was higher in premenopausal women than in postmenopausal women ( 34 ).…”