Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete gram-negative bacteria

Tom Sprong, Mihai G. Netea, Peter van der Ley, Trees J.G. Verver-Janssen, Liesbeth E.H. Jacobs, Anton Stalenhoef, Jos W.M. van der Meer, and Marcel van Deuren

General Internal Medicine, University Medical Centre, Nijmegen, Nijmegen 6500 HB

Corresponding Author: t.sprong{at}aig.umcn.nl

The use of lipoproteins has been suggested as treatment for Gram-negative sepsis, since they inhibit LPS-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed the neutralizing effect of low-denisty (LDL), high-density (HDL) and very low-density (VLDL) lipoproteins on LPS- or whole bacteria-induced cytokines in human mononuclear cells. A strong inhibition of E. coli LPS-induced IL-1beta, TNFalpha and IL-10 by LDL and HDL was seen, whereas VLDL had a less pronounced effect. In contrast, N. meningitidis LPS, in similar concentrations, was neutralized much less effectively than E. coli LPS. Effective neutralization of meningococcal LPS required a longer interaction time, a lower concentration of LPS or higher concentrations of lipoproteins. The difference in neutralization was independent of the saccharide tail, suggesting that the lipid A moiety accounted for the difference. Minimal neutralizing effects of the lipoproteins were observed on whole E. coli or N. meningitidis bacteria at all conditions tested. These results indicate that efficient neutralization of LPS depends on the type of LPS, but a sufficiently long interaction time, a low LPS-concentration or high lipoprotein concentration also inhibted cytokines by the less efficiently neutralized N. meningitidis LPS. Irrespective these differences, whole bacteria showed no neutralization by lipoproteins.

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