title: Soluble TRAIL in normal pregnancy and acute pyelonephritis: a potential explanation for the susceptibility of pregnant women to microbial products and infection.
abstract: OBJECTIVE
  Pregnancy is characterized by activation of the innate immune response demonstrated by phenotypic and metabolic changes in granulocytes and monocytes. This state of activation has been implicated in the pathophysiology of multiorgan dysfunction of pregnant women with acute viral or bacterial infection. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the mediators responsible for neutrophil apoptosis. Gene deletion of TRAIL results in delayed neutrophil apoptosis and resolution of inflammation after the administration of bacterial endotoxin. The aim of this study was to determine whether maternal plasma concentrations of the soluble form of TRAIL (sTRAIL) differ in women with uncomplicated pregnancy and those with acute pyelonephritis.
  
  
  METHODS
  A cross-sectional study was conducted to include women in the following groups: (1) non-pregnant (n = 23); (2) uncomplicated pregnancies (n = 93) and (3) pregnancies with acute pyelonephritis (n = 23). Plasma concentrations of sTRAIL were determined by enzyme-linked immunoassay.
  
  
  RESULTS
  (1) Women with uncomplicated pregnancies had a lower mean plasma sTRAIL concentration (pg/mL) than non-pregnant women (31.5 ± 10.1 versus 53.3 ± 12.5; p < 0.001); (2) plasma sTRAIL concentrations did not change as a function of gestational age (Pearson correlation = -0.1; p = 0.4); (3) the mean plasma sTRAIL concentration (pg/mL) was significantly lower in pregnant women with acute pyelonephritis than in those with uncomplicated pregnancies (20.5 ± 6.6 versus 31.5 ± 10.1; p < 0.001) and (4) among patients with acute pyelonephritis, patients with bacteremia had a significantly lower mean plasma concentration of sTRAIL (pg/mL) than those without bacteremia (15.1 ± 4.8 versus 24.7 ± 4.6; p < 0.001).
  
  
  CONCLUSIONS
  Women with uncomplicated pregnancies are associated with a significantly lower mean maternal plasma concentration of sTRAIL than that observed in non-pregnant women. Moreover, a further decrease in plasma sTRAIL concentration was observed in pregnant women with acute pyelonephritis, and this could account, at least in part, for the exaggerated intravascular inflammatory response previously reported in pyelonephritis during pregnancy.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS , Bethesda, Maryland and Detroit, MI , USA .
authors.forename: Piya
authors.initials: P
authors.lastname: Chaemsaithong
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.forename: Alyse G
authors.initials: AG
authors.lastname: Schwartz
authors.forename: Tamara
authors.initials: T
authors.lastname: Stampalija
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dong
authors.forename: Lami
authors.initials: L
authors.lastname: Yeo
authors.forename: Edgar
authors.initials: E
authors.lastname: Hernandez-Andrade
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Hassan
authors.forename: Tinnakorn
authors.initials: T
authors.lastname: Chaiworapongsa
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000009:adverse effects / Q000097:blood; D000956:Antigens, Viral / Q000009:adverse effects / Q000097:blood; D001424:Bacterial Infections / Q000097:blood* / Q000150:complications; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004198:Disease Susceptibility / Q000097:blood; D005260:Female; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000209:etiology; D011704:Pyelonephritis / Q000097:blood* / Q000209:etiology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human