Abstract 1826 Poster Session IV, Tuesday, 5/4 (poster 283)

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease (CLD) of multi-factorial origin. Cytokines have been implicated in the development of CLD. The contribution of Ureaplasma urealyticum has been debated. Steroids have improved the clinical outcome in neonates with BPD.

Aim: The purpose of this study was two-fold: firstly to investigate if Ureaplasma urealyticum could stimulate macrophages to produce proinflammatory cytokines in vitro; secondly to evaluate the downregulation of these proinflammatory cytokines by dexamethasone, budesonide and recombinant IL-10 (rIL-10).

Methods: (1). Human macrophages differentiated from a monocytic cell line (THP-1), a rat alveolar macrophage cell line (ATCC 8383) and human lung macrophage from bronchoalveolar lavage (BAL) were stimulated with Ureaplasma urealyticum antigen (4*106 -4*108 ccu/ml) or LPS (6.25-1000ng/ml) for 24 hours. (2). The same cell lines or cells were stimulated with LPS in combination with different doses of dexamethasone (10-2-10-8M) or budesonide (10-4-10-10M), or human or rat rIL-10 for 24 hours. TNFα and human IL-6 from the supernatant were measured with ELISA. Rat IL-6 was analyzed with a specific bioassay.

Results: (1).Ureaplasma urealyticum 4*106 -4*107 ccu/ml could significantly stimulate the production of TNFα and IL-6 in the human and rat alveolar macrophage cell lines. In BAL macrophages Ureaplasma urealyticum could induce a production of TNFα levels 15-85% higher than unstimulated cells. (2). Either dexamethasone, budesonide or rIL-10 could significantly inhibit the IL-6 and TNFα production in the THP-1 cell line stimulated by LPS. In the rat macrophage cell line both dexamethasone and budesonide could significantly inhibit the IL-6 and TNFα production, but rIL-10 didn't show the similar effects. Dexamethasone, budesonide and rIL-10 could inhibit TNFα production in the BAL macrophage.

Conclusion: Ureaplasma urealyticum induced a proinflammatory cytokine response and may thereby contribute to the development of CLD. Steroids and rIL-10 could be important therapeutic factors by downregulating the proinflammatory cytokines production.