Rapid induction of protective tolerance to potential terrorist agents: a systematic review of low- and ultra-low dose research^{[ * ]}

Abstract

Objective: To systematically review the literature on the ability of low-dose (LD) and ultra-low-dose (ULD) toxin exposure to prevent and treat biological and chemical threats.

Methods: Laboratory research articles on protection or treatment from LD or ULD exposure for the 13 high-risk chemical and biological warfare threats were collected and systematically evaluated for quantity and scientific quality using pre-defined methodological criteria.

Results: Over 2600 articles were screened. Only five studies met the inclusion criteria examining stimulation and protective effects of LD- or ULD-exposures to the 13 pre-identified biological and chemical agents. The quality evaluation (QE) of these studies was above average with a mean QE score of 70.6% of maximum. Two articles of fair to good quality reported both protective and treatment efficacy from exposure of animals or humans to LD- and ULD-exposures to toxins of risk in biochemical warfare.

Conclusion: There is little research on agents of biological and chemical warfare investigating the possible use of LD- and ULD-toxins for protection and treatment. The existing literature is generally of good quality and indicates that rapid induction of protective tolerance is a feasible but under-investigated approach to bioterrorist or biowarfare defense. In our opinion, further research into the role of induced protection with LD- and ULD-toxic agents is needed.

Keywords

hormesis - Low- or ultra-low dose level (exposure, response, stimulation, reverse effect) - U-shaped response - bi-phasic effect - dose-dependent reverse effects - hormoligosis - homeopathy - picopharmacology/nanopharmacology - toxicology, biological warfare agents - chemical warfare agents

^⋆ The views, opinions and assertions expressed in this article are those of the authors and do not reflect official policy of USUHS, the Department of the Army, Department of Defense, Food and Drug Administration, or the U.S. Government.

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