PT  - JOURNAL ARTICLE
AU  - Eva-Maria Boneberg
AU  - Thomas Hartung
TI  - Mistletoe Lectin-1 Increases Tumor Necrosis Factor-α Release in Lipopolysaccharide-Stimulated Whole Blood via Inhibition of Interleukin-10 Production
DP  - 2001 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 996--1000
VI  - 298
IP  - 3
4099  - http://jpet.aspetjournals.org/content/298/3/996.short
4100  - http://jpet.aspetjournals.org/content/298/3/996.full
SO  - J Pharmacol Exp Ther2001 Sep 01; 298
AB  - 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)-α 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-1β, IL-6, IL-12, and interferon-γ was not affected. Lektinol did not alter the initial phase of TNF-α production but sustained TNF-α levels longer than in the LPS controls. Recombinant ML-1, but not the recombinant B-chain alone, also increased TNF-α release and decreased IL-10 release. We propose that the increase in TNF-α 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-α 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-α 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. The American Society for Pharmacology and Experimental Therapeutics