Ureaplasma urealyticum Modulates Endotoxin-Induced Cytokine Release by Human Monocytes Derived from Preterm and Term Newborns and Adults
AUTOR(ES)
Manimtim, Winston M.
FONTE
American Society for Microbiology
RESUMO
We previously observed that Ureaplasma urealyticum respiratory tract colonization in infants with a birth weight of ≤1,250 g was associated with increases in the tracheal aspirate proinflammatory cytokines tumor necrosis factor alpha (TNF-α) 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-α, 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 (103 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-α and IL-8 release by preterm cells, and (iii) augmented LPS-stimulated TNF-α release in all cells. In preterm cells, high-inoculum U. urealyticum (106 CCU) (i) stimulated TNF-α and IL-8, but not IL-6 or IL-10, release and (ii) augmented LPS-stimulated TNF-α 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-α, 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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=98421Documentos Relacionados
- Inhibition of endotoxin-induced activation of human monocytes by human lipoproteins.
- Heparin and enoxaparin enhance endotoxin-induced tumor necrosis factor-alpha production in human monocytes.
- Modulation of endotoxin-induced monokine release in human monocytes by lipid A partial structures that inhibit binding of 125I-lipopolysaccharide.
- Prevention of endotoxin-induced monokine release by human low- and high-density lipoproteins and by apolipoprotein A-I.
- Neutralization of bacteria- and endotoxin-induced hypotension by lipoprotein-free human serum.