Many of the adverse events surrounding the birth of a child are associated with inflammation, including acute and chronic neonatal lung disease. Administration of parenteral dexamethasone (Dex) to infants with bronchopulmonary dysplasia (BPD) is associated with a reduced need for mechanical ventilation. Administration of Dex to infants with more acute lung disease is associated with a reduction in the incidence of (BPD). One mechanism whereby Dex likely decreases pulmonary disease is by reducing inflammation. Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh), two genital mycoplasmas, are the most common organisms isolated in the perinatal period and both either cause or are associated with neonatal lung disease. We have shown in an animal model that these microbes cause inflammation, composed mainly of macrophages, and in vitro they stimulate macrophages to produce TNFα and iNOS. We hypothesized that Dex would decrease the production of these inflammatory mediators in a dose-dependent fashion. RAW 264.7 cells, a murine macrophage cell line, were incubated for 16 hours with sterile media (control) or LPS (10ng/ml, 100ng/ml), Uu or Mh (104, 105,106 cfu/ml). TNFα was measured by ELISA (Endogen, Inc.). LPS, Uu, and Mh all induced TNFα production in a dose-dependent fashion (p < 0.05). Incubating the macrophages with Dex (10-6, 10-8, 10-10 M) concurrently with either LPS, Uu or Mh reduced the TNFα production in a dose-dependent fashion (p < 0.05). A 4 hr preincubation with Dex further decreased the TNFα production (p < 0.05). Immunoelectrophoresis was used to measure iNOS. Incubation of the macrophages with 10U IFN gamma and either LPS, Uu or Mh produced iNOS in a dose-dependent fashion. Preincubation of macrophages with Dex 10-6 M for 24 hours significantly decreased iNOS production. Our results demonstrate that Dex significantly reduces the production of the inflammatory mediators TNFα and iNOS from macrophages. We speculate that this effect might be part of the process whereby Dex decreases the severity of neonatal lung disease.
