Abstract
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.
Footnotes
- Abbreviations:
- ML
- mistletoe lectin
- LPS
- lipopolysaccharide
- ELISA
- enzyme-linked immunosorbent assay
- rAB
- recombinant mistletoe lectin-1 heterodimer
- TNF
- tumor necrosis factor
- IL
- interleukin
- IFN
- interferon
- PBS
- phosphate-buffered saline
- Received March 2, 2001.
- Accepted May 17, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|