Allotypic Immuno-Modulators (AIMs)

Many natural products and their derived compounds also function medicinally as Immunomodulators, and do so effectively without the toxicity and expense associated with the BRMs produced by biotechnology and biopharmaceutical firms.  An important feature among several of the natural products Immunomodulators is their tendency to demonstrate a “balancing” effect, as opposed to simply upregulating or downregulating the human immune response. 

A great deal of interest has been focused upon a number of bioactive polysaccharides which have been shown to possess promising utility in modifying innate immune responses [ 19 ] .  Clinical and laboratory studies have demonstrated activity upon both innate and adaptive immune system functions, and polysaccharide receptors have been found on several types of immune and inflammatory cells, including NK cells, T- and B-lymphocytes, macrophages, and monocytes [ 20 ] .

Thus, advanced research in Immunotherapy is now focusing primary attention on the investigation and clinical application of purified polysaccharides of high-specificity, which can function reliably as Allotypic Immuno-Modulators (AIMs).  Bioactive polysaccharides derive from many sources—e.g., higher plants, fungi and bacteria—which produce a diversity of molecular classes, including Arabinoxylans, β-D -Glucans, and proteoglycans.   Among these, oligo-arabinoxylans, polysaccharide-A (PSA; fig. 1) and polysaccharide-K (PSK) have been studied extensively in laboratory and clinical investigations, with the most promising recent results coming from studies on purified, high-specificity, rice bran oligo-arabinoxylan compounds.

Allotypic Immuno-Modulator (AIM) anti-cancer strategies can provide a significant therapeutic advantage in combating tumorigenesis at the pre-cancer, or initiation stage, as well as the pre-clinical and clinical stages of promotion and proliferation, via their activation of Natural Killer cell cytotoxicity.

Oligo-Arabinoxylan Compounds 

  Previous in vitro and in vivo studies have demonstrated that a purified, high-specificity, oligo-arabinoxylan AIM derived from rice bran (Rice Bran Arabinoxylan Compound, RBAC ; fig. 2) modulates NK, T- and B-cell immune cell functions in a dose-dependent manner.

Figure 2 :  A ball-and-stick molecular model
of the AIM oligo-arabinoxylan, RBAC.

Incubation of peripheral blood lymphocytes (PBLs) with RBAC induced increases in NK cell cytotoxicity in PBLs showing low baseline NK cytotoxic activity, while decreasing activity in PBLs with high baseline NK cytotoxic activity [21 ].  In a later study, RBAC was further found to sensitize human T-cell leukemia cells (HUT 78) to CD95 death receptor-induced apoptosis [22 ].  

RBAC also has been shown to possess anti-oxidant properties as a free-radical scavenger; optimizing the production of inflammatory cytokines IFN-γ, TNF-α and IL-6; increasing nitrous oxide release and the overall phagocytic activity of macrophages [ 23-25 ] .  Published human trial data from a Rheumatoid Arthritis case series in Japan also demonstrated anti-inflammatory activity of RBAC in close to 50% of subjects when administered over a 6-12 month period [ 26 ] .

Together these findings established RBAC as a broad-spectrum immunomodulator and anti-inflammatory agent worthy of clinical investigation and application in the management of the several aging-related diseases and disorders which are of an immunosenescence etiology.

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