Vol. 298, Issue 3, 996-1000, September 2001

Mistletoe Lectin-1 Increases Tumor Necrosis Factor- Release in Lipopolysaccharide-Stimulated Whole Blood via Inhibition of Interleukin-10 Production

Eva-Maria Boneberg and Thomas Hartung

Biochemical Pharmacology, University of Konstanz, Konstanz, Germany

We examined the immunomodulatory properties of the mistletoe preparation Lektinol (standardized for mistletoe lectin-1) and recombinant mistletoe lectin-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 release in unstimulated whole blood. However, the lipopolysaccharide (LPS)-induced release of tumor necrosis factor (TNF)- was increased, and the secretion 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 secretion of IL-1, IL-6, IL-12, and interferon- was not affected. Lektinol did not alter the initial phase of TNF- production but sustained TNF- levels longer than in the LPS controls. Recombinant ML-1, but not the recombinant B-chain alone, also increased TNF- release and decreased IL-10 release. We propose that the increase in TNF- release is due to a specific inhibition of IL-10 release by Lektinol. This conclusion is based on the observation that blocking of endogenously formed IL-10 by a neutralizing antibody results in a similar increase of TNF- in the late production phase after LPS stimulation. This hypothesis was also corroborated by the finding that when endogenously formed IL-10 was blocked, Lektinol could no longer increase TNF- release. These results indicate that Lektinol modulates the cytokine response of human whole blood to LPS in a proinflammatory fashion, which can be attributed to ML-1.