title: Ureaplasma urealyticum modulates endotoxin-induced cytokine release by human monocytes derived from preterm and term newborns and adults.
abstract: We previously observed that Ureaplasma urealyticum respiratory tract colonization in infants with a birth weight of < or =1,250 g was associated with increases in the tracheal aspirate proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) relative to the counterregulatory cytokine IL-6 during the first week of life (A. M. Patterson, V. Taciak, J. Lovchik, R. E. Fox, A. B. Campbell, and R. M. Viscardi, Pediatr. Infect. Dis. J. 17:321-328, 1998). We hypothesized that U. urealyticum alters the host immune response in the presence of a coinflammatory stimulus (e.g., bacterial infection or hyperoxia) by shifting the balance of cytokine expression towards the proinflammatory cytokines. To test this hypothesis, we compared the release of TNF-alpha, IL-8, IL-6, and IL-10 in vitro by unstimulated and U. urealyticum (with or without lipopolysaccharide [LPS])-stimulated human monocytes from adult peripheral blood and from term and preterm cord blood. U. urealyticum alone and in combination with LPS induced concentration- and development-dependent changes in cytokine release. In vitro inoculation with low-inoculum U. urealyticum (10(3) color-changing units [CCU]) (i) partially blocked the LPS-stimulated IL-6 release by all cells and reduced LPS-stimulated IL-10 release by preterm cells, (ii) stimulated TNF-alpha and IL-8 release by preterm cells, and (iii) augmented LPS-stimulated TNF-alpha release in all cells. In preterm cells, high-inoculum U. urealyticum (10(6) CCU) (i) stimulated TNF-alpha and IL-8, but not IL-6 or IL-10, release and (ii) augmented LPS-stimulated TNF-alpha and IL-8 release. High-inoculum U. urealyticum (i) stimulated release of all four cytokines in term cells and IL-8 release in adult cells and (ii) augmented LPS-induced TNF-alpha, IL-10, and IL-8 release in term cells but did not significantly affect LPS-induced cytokine release in adult cells. We speculate that U. urealyticum enhances the proinflammatory response to a second infection by blocking expression of counterregulatory cytokines (IL-6 and IL-10), predisposing the preterm infant to prolonged and dysregulated inflammation, lung injury, and impaired clearance of secondary infections.
authors.affiliation: Departments of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Manimtim
authors.forename: J D
authors.initials: JD
authors.lastname: Hasday
authors.forename: L
authors.initials: L
authors.lastname: Hester
authors.forename: K D
authors.initials: KD
authors.lastname: Fairchild
authors.forename: J C
authors.initials: JC
authors.lastname: Lovchik
authors.forename: R M
authors.initials: RM
authors.lastname: Viscardi
mesh_terms: D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D016869:Ureaplasma Infections / Q000382:microbiology; D016990:Ureaplasma urealyticum / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides