[Immunomodulating mistletoe therapy by lectin standardization: a double-edged sword?]

Taking advantage of an unique, legally generous regulation, proprietary anthroposophic and phytotherapeutic mistletoe preparations are on the market in Germany. One constituent of the extract, the galactoside-specific lectin, is a potent biological response modifier in a very narrow low-dose range. Although the clinical implications of the lectin effects remain to be rigorously defined, this activity already prompted companies to eliminate the common batch-to-batch variations in favor of standardization, keeping the lectin content, which could otherwise vary drastically, purportedly constant. Based on literature data, immunomodulation by the lectin involves enhanced secretion of multifunctional proinflammatory cytokines such as IL-6. The apparently context-dependent ambivalence of their actions includes capacity to serve as autocrine and paracrine tumor growth and survival factors for a wide variety of tumor cell types in vitro and in vivo, as illustrated by the literature presented. The potential for clinical risks is indicated to be non-negligible, e.g. for lymphomas, advanced-stage melanomas and renal cell carcinomas. Moreover, negative effects of immunomodulatory lectin or extract treatment have already been reported. To reliably prove clinical efficacy and exclude lack of undesired side effects for each tumor class and stage, it is mandatory to evaluate the performance of this experimental therapy modality exclusively in relevant preclinical settings and strictly controlled clinical studies to obey the generally accepted rule: primum non nocere.