Central but not the peripheral action of cholinergic compounds suppresses the immune system

Cholinergic compounds modulate the immune system; however, the mechanism of cholinergic immunotoxicity is largely unknown. Lewis rats were exposed chronically to cholinergic compounds via subcutaneous or intracerebroventricular routes. Compounds that crossed the blood-brain barrier (BBB) inhibited the antibody response when given by either route, however, poorly permeable compounds, unless given in high doses, inhibited the antibody response only by intracerebroventricular administration. Intracerebroventricular administration of cholinergic agents also reduced serum corticosterone levels, which along with the antibody response was attenuated by pretreatment with the ganglionic blocker chlorisondamine. Thus, cholinergic agents affect the neuroimmune communication and inhibit glucocorticoid production; the latter may be a biomarker for cholinergic toxicity.