Natural Immune Modulation and Biodefenses
Stephen Holt, MD, LLD(Hon.), ChB, PhD, DNM, FRCP (C), MRCP (UK), FACP, FACG, FACN, FACAM. Distinguished Professor of Medicine, NYCPM, NY, Gitte S. Jensen, PhD, and Aaron N. Hart, PhD, Research Scientists, NIS Inc., Canada and Oregon

While immune function involves a complex cascade of bio-physiological events, attempts to enhance or modulate immunity, using natural medicines, has often focused inappropriately on the use of single agents of botanical or nutrient origin. Practitioners of Integrative Medicine have placed much confidence in natural substances that may increase Natural Killer cell function (NK cell activity), without sufficient consideration for many other aspects of immunity, such as B cell activity, antibody function and messenger molecule cascades (e.g. interleukins). To test the hypothesis that complex immune functions require synergistic formulations of multiple, herbs, botanicals and nutrients, a complex formulation of natural agents with a variable evidence base for altering immune function (Formulation A) were compared with a less complex version of a natural immune modulating product composed of a blend of fermented rice bran and shiitake mycelium extract the (most popular immune stimulator used in Integrative Medical practice in the past decade) (Formulation B). Formulation A and B were purchased over the counter as dietary supplements and compared in experiments to define effects on several parameters of immune function.

Methods: A selected panel of standard in vitro assays for lymphocyte activation was used on cell cultures of freshly isolated human lymphocytes from healthy donors. Direct NK activation was evaluated by immunostaining and flow cytometry for the NK cell activation markers CD69, CD25, and CD54. Proliferation of B, T, and NK cell subsets in vitro was monitored by a flow cytometric method. Cytokine production was evaluated by intracellular staining for TNF-alpha and Interferon-gamma, as well as enzyme-linked immunosorbent assays for Interferon-gamma.

Results and Conclusions: Culturing of human lymphocytes in the presence of Formulation A resulted in a strong direct activation of NK cells, as evaluated by induction of CD69 on almost 100% peripheral blood NK cells. The effect was concentration-dependent, but substantial NK cell activation was seen over a broad range of dilutions. Formulation B produced a weaker, but consistent, activation of NK cells in vitro. Comparison of serial dilutions of both extracts showed that induction of the CD69 NK activation marker required 10-100 fold higher concentrations of Formulation B extract in order to produce similar activation levels as the Formulation A. Neither of the two extracts possessed mitogenic activity, but Formulation A was able to modulate responses to the known T cell mitogen PHA, by reducing PHA-induced proliferation.

This study supports the notion that versatile changes in immune status require comprehensive combinations of synergistic agents that affect a range of the complex cascades of immune function. Furthermore, these findings demonstrate the need for purveyors of professional dietary supplements to provide specific research information on their products, rather than the promotion of a product by the use of borrowed science or inference.

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