Induction of Human Neonatal Pulmonary Fibroblast Cytokines by Hyperoxia and Ureaplasma urealyticum

Multiple insults may induce bronchopulmonary dysplasia (BPD) in premature infants, including the recently reported association of BPD with neonatal Ureaplasma urealyticum colonization. One mechanism of damage could involve stimulation of proinflammatory cytokine release from pulmonary fibroblasts. We therefore compared the effects of U. urealyticum, oxygen, and lipopolysaccharide (LPS) on the release of interleukin (IL)-1β, IL-6, and IL-8 from neonatal fibroblasts. Fibroblasts were grown in multiwell plates and divided into the following experimental conditions: fibroblasts alone, fibroblasts plus U. urealyticum (10,000 cfu/mL), and fibroblasts plus LPS (2 µg/mL). Plates were then exposed to room air or hyperoxia for 48 h, and supernatants were assayed for IL. U. urealyticum-infected fibroblasts produced a significant increase in IL-6 (P <.05) and a dramatic increase in IL-8 (P <.05) that was independent of hyperoxic exposure and significantly increased over that produced by LPS or hyperoxia alone. U. urealyticum is a potent inducer of fibroblast cytokine release in vitro and may contribute to the development of BPD.