ABSTRACT
OBJECTIVE: This study examined the effect of dehydroepiandrosterone (DHEA) on lipopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) production in the DH82 canine macrophage cell line. STUDY DESIGN: Cultured DH82 cells were stimulated with varying concentrations of LPS with or without DHEA for various times. Supernatant IL-6 levels were measured by enzyme-linked immunosorbent assay, and cellular cytoplasmic IkappaBalpha protein expression measured by Western blot analysis. RESULTS: LPS dose-dependently stimulated IL-6 production (p=0.016). Cells stimulated with 20 microg LPS showed a time-dependent increase of IL-6 concentration up to 10 h post-treatment (p=0.007). Co-treatment of DH82 cells with 20 microg LPS and various concentrations of DHEA for 14 h showed that up to 10 microM DHEA dose-dependently decreased the IL-6 concentration (p=0.007). Also, addition of 20 microM DHEA to DH82 cells with 20 microg LPS time-dependently decreased the IL-6 concentration for up to 14 h post-treatment (p=0.018). Stimulation of cultured DH82 cells with 20 microg LPS significantly decreased cellular cytoplasmic IkappaBalpha expression, beginning at 30 min post-treatment and persisting to at least 2 h post-treatment (p=0.012). However, co-treatment of cells with 20 microg LPS and 20 microM DHEA abrogated this effect until 2 h post-treatment. CONCLUSIONS: DHEA decreased the IL-6 concentration in the supernatant of LPS-stimulated DH82 cells by inhibiting the sequestration of IkappaBalpha, which is necessary for the activation of nuclear factor-kappa B. These findings provide new insights into the immunomodulatory effects of DHEA.
Subject(s)
Dehydroepiandrosterone/pharmacology , Interleukin-6/biosynthesis , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Animals , Cell Line , Cells, Cultured , Dogs , Drug Interactions , I-kappa B Proteins/biosynthesis , Interleukin-6/immunology , Macrophages/immunology , NF-KappaB Inhibitor alpha , NF-kappa B/metabolismABSTRACT
OBJECTIVES: To determine the effectiveness and clinical utility of antenatal corticosteroids in the reduction of neonatal morbidity and mortality on preterm birth Material and method: Neonatal outcomes of 312 preterm babies were evaluated retrospectively. One hundred and two preterm babies(study group) were given dexamethasone more than 1 dose antenatally and 210 preterm babies(control group) were not given dexamethasone antenatally. Antenatal steroids were administered in the form of four 5mg intramuscular doses of dexamethasone 12 hours apart. Maternal and neonatal outcomes of study group were compared with those of control group. Student t- test, x2 test, Fisher's exact test, and logistic regression analysis were used where appropriate. p-value< 0.05 was considered significant. RESULTS: Antentenatal corticosteroid significantly decreased the incidence of RDS(OR:0.47, 95% CI:0.25-0.86), IVH/PVL(OR : 0.32, 95% CI : 0.12-0.86), necrotizing enterocolitis(OR : 0.49, 95% CI : 0.25-0.98), and neonatal death(OR: 0.30, 95% CI: 0.10 - 0.89) in preterm delivery. In the presence of PROM, antenatal corticosteoid seemed to have no protective effect on the neonatal complications such as RDS, IVH/PVL, NEC, PDA, and neonatal death. CONCLUSIONS: Antenatal administration of corticosteroids was effective to decrease the incidence of neonatal morbidity and neonatal mortality in the preterm neonates with no apparent maternal complications.
