Wm. Manimtim et al., Ureaplasma urealyticum modulates endotoxin-induced cytokine release by human monocytes derived from preterm and term newborns and adults, INFEC IMMUN, 69(6), 2001, pp. 3906-3915
We previously observed that Ureaplasma urealyticum respiratory tract coloni
zation in infants with a birth weight of less than or equal to1,250 g was a
ssociated 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, Vis
cardi, Pediatr. Infect, Dis, J, 17:321-328, 1998), We hypothesized that U.
urealyticum alters the host immune response in the presence of a coinflamma
tory stimulus (e.g,, bacterial infection or hyperoxia) by shifting the bala
nce of cytokine expression towards the proinflammatory cytokines, To test t
his 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 lipopolysacch
aride [LPS])-stimulated human monocytes from adult peripheral blood and fro
m term and preterm cord blood, U, urealyticum alone and in combination with
LPS induced concentration- and development-dependent changes in cytokine r
elease. In vitro inoculation with low-inoculum U. urenlyticum (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, (i
i) stimulated TNF-alpha and IL-8 release by preterm cells, and (iii) augmen
ted LPS-stimulated TNF-at release in all cells. In preterm cells, high-inoc
ulum 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 si
gnificantly affect LPS-induced cytokine release in adult cells. We speculat
e that U. urealyticum enhances the proinflammatory response to a second inf
ection by blocking expression of counterregulatory cytokines (IL-6 and IL-1
0), predisposing the preterm infant to prolonged and dysregulated inflammat
ion, lung injury, and impaired clearance of secondary infections.