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Activation of the Cholinergic Antiinflammatory Pathway Reduces Ricin-Induced Mortality and Organ Failure in Mice 

Our results have demonstrated that nicotine reduces organ failure and improves mouse survival following ricin exposure. The protective effect of nicotine appears to be associated with its antiinflammatory effect, suggesting a possible therapeutic strategy of activating the cholinergic antiinflammatory pathway following ricin exposure to protect against multiple organ failure. Nicotine treatment reduced levels of the inflammatory cytokine TNF-•and improved both liver and kidney function while reducing the oxidative stress observed in these organs following ricin exposure. The overall effect of nicotine on maintaining liver and kidney function while reducing systemic inflammation may account for the reduced mortality observed with ricin exposure.

Ricin has been shown to induce a severe inflammatory response that has been linked to development of acute renal failure (5,6). Ricin exposure also . . .

The protection against ricin-mediated inflammation and systemic organ failure by nicotine is likely due to the antiinflammatory effect of nicotine-blocking NF-•B activation and inflammatory gene expression. . . .

Currently there is no antidote to ricin, and the treatment options following exposure consist of providing supportive measures to maintain organ function and removing the toxin from the body. Therefore, the development of new therapies that maintain organ function and delay mortality following ricin poisoning would be invaluable both for accidental and deliberate exposure of the human population. The data presented here suggest activation of the cholinergic antiinflammatory pathway may prove to be an effective therapeutic strategy to improve survival following ricin exposure. This effect may be induced centrally, by stimulating the vagus nerve or inhibiting cholinesterases, or peripherally, using nicotine or a specific alpha7nAChreceptor agonist.

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