Biological effects of natural and recombinant mistletoe lectin and an aqueous mistletoe extract on human monocytes and lymphocytes in vitro

Mistletoe lectin is thought to constitute the active principle in extract p reparations from mistletoe, which are widely used as immunomodulators in ad juvant tumor therapy. However, no study exists which compares the immunolog ical potency of different well-defined mistletoe lectin preparations on hum an immune cells. Therefore, in the present study the biological effects of an aqueous mistletoe extract, standardized for mistletoe lectin I (eML), th e isolated natural mistletoe lectin (nML), and the recombinant form of this lectin (rML) on human peripheral blood monocytes and lymphocytes were comp ared with respect to cell viability and cytokine induction. After 48-hr inc ubation of peripheral blood mononuclear cells (PBMC) with rML, nML, and eML , a continuous concentration-dependent decrease in cell viability was found with an IC50 of about 3 ng/ml for rML and nML and 10 ng/ml for eML, respec tively. This effect also was seen when isolated lymphocytes and monocytes w ere separately incubated with the lectin preparations. After incubation of PBMC and isolated monocytes of 5/10 brood donors with eML, an increase in c ell viability was found at lectin concentrations between 10 and 1,000 pg/ml . This effect was not seen with the pure lectin preparations nML and rML. A fter 48-hr incubation of PBMC with rML, nML, and eML, induction of IL-1-bet a, TNF-alpha, IL-2, IL-6, and IL-10 but not IFN-gamma was measured. For IL- 1-beta it could be shown that cytokine induction took place at a broad lect in concentration range (0.1-100 ng/ml). Cytokine levels varied greatly in t he PBMC cultures of the different blood donors. When monocytes were separat ely incubated with eML, nML, and rML for 48 hr, high levels of IL-1-beta we re found. In contrast, in cultures of separated lymphocytes from the same d onors only a minimal production of IL-1-beta and no production of IFN-gamma was found after incubation with rML, nML, and eML. It is concluded that th ere are quantitative differences in the immunomodulatory effects of the mis tletoe lectin preparations on human monocytes and lymphocytes. Therefore, m easurement of cell viability and cytokine induction may be a diagnostic lab oratory tool to determine the immunological potency of various mistletoe pr eparations and may help to clarify the clinical benefit of therapies with t hese substances. J. Clin. Lab. Anal. 14:255-259, 2000. (C) 2000 Wiley-Liss, Inc.