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 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)-alpha 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 beta, IL-6, IL-12, and interferon-gamma was not affected. Lektinol did not alter the initial phase of TNF-alpha production but sustained TNF-alpha levels longer than in the LPS controls. Recombinant ML-1, but not the recombinant B-chain alone, also increased TNF-alpha release and decreased IL-10 release. We propose that the increase in TNF-alpha 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-alpha 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-alpha 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.
Boneberg
E M
EM
Biochemical Pharmacology, University of Konstanz, Konstanz, Germany.
Hartung
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008033:Limulus Test; D008070:Lipopolysaccharides / Q000494:pharmacology*; D028321:Plant Preparations; D010940:Plant Proteins; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D028321:Plant Preparations; D010940:Plant Proteins; D011994:Recombinant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; D014409:Tumor Necrosis Factor-alpha; C009674:ribosome inactivating protein, Viscum; D016753:Interleukin-10