History & Background

The unassembled original concepts that underpin ImmuneACCORD™ were readily available in the historical and science record of discovery. Visit: "Publications" for supporting documentation. While the work listed below chiefly inspired ImmuneACCORD technology many paths to knowledge and many other investigators cited in these reviews and elsewhere are of tremendous importance.

Article & Reviews:
(1) Proposing a major role for inflammation in chemical toxicity predicted design of Multi-Threat Medical Countermeasures (MTMC) technology to interdict the common inflammatory pathology for multiple classes of chemical agents and further improve public health (Cowan et al. 1993, 1996; 2003; 2004). Such broad spectrum chemical countermeasures were later incorporated as a component of Homeland Security Presidential Directive/HSPD-18.

(2) An area of special interest but limited experimentation and information is the synergistic action of combinations of naturally occurring bioactive molecules such as phytonutrients in phytotherapy and anti-inflammatory drugs (Haines et al., 2000; reviewed, Martins 2006).

(3) Aggarwal and Shishoda (2004) review the link between NF-kappaB inflammatory pathway and diseases and the NF-kappaB inhibitory pharmacology and anti-inflammatory properties of phytochemicals derived from spices such as capsaicin (hot peppers) and curcumin (curry).

(4) McCarty (2004) suggested "Multifocal Signal Modulation Therapy" for targeting signaling pathways as a strategy for managing cancer. This encompassed up-regulation of certain oncogenic signaling pathways that promote proliferation, inhibit apoptosis, and enable the cancer to spread and evoke angiogenesis. McCarty proposed the feasible of decreasing the activity of pathological pathways–or increasing the activity of pathways that oppose them using noncytotoxic agents to include synergistic combinations of natraceuticals. Such therapy should further augment standard cytotoxic agents used in cancer therapy.

(5) Martin (2006) has written a comprehensive review of the complex process of apoptosis, a form of "adaptive cell death", and how the apoptotic action of the NF-kappaB pathway inhibitory natraceuticals can act as a pivotal defense against disease and pathological inflammation. Apoptotic pharmacology is commonly seen in chemical agent countermeasures and predicted as a MTMC strategy (Cowan et al. 2006).

Microsc Res Tech. 2002 Nov 15;59(4):264-72.
Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction.
Chung HY, Kim HJ, Kim KW, Choi JS, Yu BP.
College of Pharmacy, Pusan National University, Pusan 609-735, Korea. hyjung@pusan.ac.kr

Accumulating evidence strongly suggests that oxidative stress underlies aging processes. Research provides consistent evidence that calorie restriction (CR) reduces age-related oxidative stress and has anti-inflammatory properties. However, information is lacking on the molecular mechanism that would better define the interrelation of reactive oxygen species and nitrogen species and the pro-inflammatory states of the aging process. In this review, the biochemical and molecular bases of the inflammatory process in the aging process are analyzed to delineate the molecular inflammation hypothesis of aging. The key players involved in the proposed hypothesis are the age-related upregulation of NF-kappa B, IL-1 beta, IL-6, TNFalpha, cyclooxygenase-2, and inducible NO synthase, all of which are attenuated by CR. Furthermore, age-related NF kappa B activation is associated with phosphorylation by I kappa B kinase/NIK and MAPKs, while CR blocked these activation processes. The modulation of these factors provides molecular insights of the anti-inflammatory action of CR in relation to the aging process. Based on available finding and our recent supporting evidence, we prefer to use "molecular inflammation" to emphasize the importance of the molecular reaction mechanisms and their aberrance, predisposing to fully expressed chronic inflammatory phenomena. It was further proposed that CR's major force of the regulation of redox-sensitive inflammation may well be its life-prolonging action. Copyright 2002 Wiley-Liss, Inc.

Also see "Physicians and Scholars Cooperation Group".