Impaired leukotriene B4 release by neonatal polymorphonuclear leukocytes

Leukotriene B4 (LTB4) is a potent mediator of inflammation generated by polymorphonuclear leukocytes (PMN) in response to an appropriate stimulus. It acts as a chemoattractant and stimulates PMN functions, amplifying their inflammatory response. Newborn infants show an increased susceptibility to infections in which PMN dysfunctions play the main role. In this work, LTB4 release from neonatal polymorphonuclear cells was assessed to investigate whether a defect was detectable. Blood was obtained from the umbilical cord of 10 full-term healthy neonates and 10 adult controls. The LTB4 production from purified PMN suspensions was induced by three different stimuli: the calcium ionophore A23187, serum-treated zymosan, and formyl-methionyl-leucyl-phenylalanine at final concentrations of 2 microM, 10 mg/mL, and 10 microM, respectively. The kinetics of LTB4 release were studied for up to 30 min by assaying the supernatants of the stimulated cells with a specific RIA. The LTB4 release, undetectable in resting PMN, was strongly stimulated by the A23187, peaking at 5 min, with significantly higher levels (t test, p < 0.01) in newborn than in adult PMN preparations (mean +/- SD: 12.46 +/- 2.96 and 6.21 +/- 2.09 ng/10(6) cells, respectively). In comparison, serum-treated zymosan-stimulated PMN released smaller amounts of LTB4. The levels peaked at 10 min and were significantly (t test, p < 0.01) lower in newborn than in adult samples (mean +/- SD: 0.71 +/- 0.22 and 3.19 +/- 1.06 ng/10(6) PMN, respectively). Finally, when the PMN were stimulated by formyl-methionyl-leucyl-phenylalanine, the release of LTB4 was highly variable both in newborn and in adult samples, as previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)