Links between multiple chemical sensitivity and asthma in a rat model of cholinergic hypersensitivity: a brief review

Abstract

Individuals with multiple chemical sensitivity (MCS) also commonly report symptoms of asthma, but, as far as we have been able to determine, no one has yet suggested that an abnormal cholinergic system may provide the link between asthma and MCS. The present brief review provides evidence for such a link by summarizing recent findings in a genetic animal model of cholinergic hyperresponsiveness. The Flinders Sensitive Line (FSL) rats were developed by selective breeding for increased responses to an anticholinesterase agent similar to commonly used organophosphate pesticides. Relative to their control line, the Flinders Resistant Line (FRL) rats, the FSL rats are more sensitive to drugs that stimulate acetylcholine receptors, alcohol, diazepam, and drugs that have a selective effect on dopamine or serotonin receptors. These findings raise the possibility that the FSL rats may resemble individuals with MCS. Hyperresponsiveness of the airways is a hallmark of asthma. The procedure known as whole-body plethysmography, where breathing can be monitored in freely moving animals, was employed to study the FSL and FRL rats. The FSL rats exhibited a greater index of bronchoconstriction than the FRL rats in response to both a cholinergic agonist and an allergen challenge. Thus, the FSL rats are more sensitive both to a variety of drugs unrelated to the cholinergic system and to cholinergic- and allergen-induced bronchoconstriction. An abnormal cholinergic system may therefore contribute to both MCS and asthma.