Mistletoe lectin-1 increases tumor necrosis factor-alpha release in lipopolysaccharide-stimulated whole blood via inhibition of interleukin-10 production

We examined the immunomodulatory properties of the mistletoe preparation Le ktinol (standardized for mistletoe lectin-1) and recombinant mistletoe lect in-1 (rML-1) in vitro by assessing alterations in the cytokine response of human whole blood. Lektinol or rML-1 alone did not induce any cytokine rele ase in unstimulated whole blood. However, the lipopolysaccharide (LPS)-indu ced release of tumor necrosis factor (TNF)-alpha was increased, and the sec retion of interleukin (IL)-10 was reduced by Lektinol at a mistletoe lectin -1 (ML-1) concentration of 0.5 to 5 ng/ml, whereas the LPS-induced secretio n of IL-1 beta, IL-6, IL-12, and interferon-gamma was not affected. Lektino l did not alter the initial phase of TNF-alpha production but sustained TNF -alpha levels longer than in the LIPS controls. Recombinant ML-1, but not t he recombinant B-chain alone, also increased TNF-alpha release and decrease d IL-10 release. We propose that the increase in TNF-alpha release is due t o a specific inhibition of IL-10 release by Lektinol. This conclusion is ba sed on the observation that blocking of endogenously formed IL-10 by a neut ralizing antibody results in a similar increase of TNF-alpha in the late pr oduction phase after LPS stimulation. This hypothesis was also corroborated by the finding that when endogenously formed IL-10 was blocked, Lektinol c ould no longer increase TNF-alpha release. These results indicate that Lekt inol modulates the cytokine response of human whole blood to LPS in a proin flammatory fashion, which can be attributed to ML-1.