Immunmodulatory Effects of LPS of Clinically Relevant Pathogens to the Fetale Immune System in Pregnancy

The aim of our study was to investigate the role of gram negative bacteria frequently found in cervical swabs of pregnant women causing premature labor, rupture of membrance and premature delivery. Therefore, we stimulated cord blood PBMCs from mature pregnancies with purified LPS of E. coli, Klebsiella pneu., Proteus mir., Enterobacter aer., Acinetobacter cal., Citrobacter fr. and Pseudomonas aer. for 4h and 36h to determine the secretion of a broad panel of immunologically relevant cyto- and chemokines.

In fetal blood we found IL–6, TNF, IL–1ß (pro-inflammatory-), IL–10, IL–13 (anti-inflammatory-), INF-y, IL12p40/p70 (TH₁-polarizing-cytokines), IL–8, MCP–1, MIP–1a and MIP–1ß (chemokines) upon stimulation with all LPS. In contrast, none of the tested LPS variants activated cord blood cells for the release of IL–2, IL–7, IL–15, IL–17, IFN-a, GM-CSF, IP–10, VEGF, G-CSF, EGF, FGF- and HGF. Concluding, LPS of different gram-negative bacteria revealed different innate immune activation in cord blood and therefore may be considered as more or less clinically aggressive. LPS of Enterobacter aerogenesa and E.coli revealed the strongest capacity for highest production of cytokines and chemokines, whereas LPS of Pseudomonas aeruginosa induced only a variable, delayed cytokine-release. LPS of Klebsiella pneumoniae induced the most rapid cytokine secretion. Concerning special cinetics the TNF-and IL12p40/p70-peak of release was in all tested LPS-variants after four hour incubation extremely elevated compared to 36 hours incubation.

Future aims are the in vitro treatment of LPS-stimulated PBMCs with indomethacin combined with bethamethason followed by determination of inhibition of cytokine release.

Immunmodulation LPS Fetal Immune System Pregnancy