An investigation into the role of the parasympathetic nervous system in modulating the response of sheep to endotoxin : dissertation submitted in partial fulfilment of the requirements for the degree of Bachelor of Science with Honours at Lincoln University

Abstract

The parasympathetic nervous system has recently been implicated in the modulation of systemic inflammatory responses to endotoxin. Evidence for this anti-inflammatory role is based on in vitro studies of human macrophages and in vivo studies with rats (Borovikova et al., 2000a). To test the hypothesis that a similar pathway operates in sheep, we subjected sheep to endotoxin challenge after prior modification of parasympathetic function with either atropine or pilocarpine.

Three groups of adult ewes (n = 8) each received (as an i.m. injection at 90, 210 and 330 minutes) one of the following treatments: saline, atropine sulphate (0.3 mg/kg) or pilocarpine hydrochloride (0.4 mg/kg). Three more groups (n = 8) received the same three treatments with the addition of 400 ng/kg endotoxin (lipopolysaccharide derived from E. coli) delivered by i.v. injection at 120 minutes. Body temperature, heart rate, haematocrit, blood glucose concentration and pupil size were monitored for seven hours.

Elevations in heart (atropine) and body temperature (pilocarpine) confirmed that the drugs used here had been delivered at pharmacological doses, but there was no effect of either compound on the magnitude of the endotoxin-induced fever. However, pilocarpine on its own produced a fever, so it was expected that a significant elevation of body temperature would result, above that produced by endotoxin alone, when the two treatments were combined. This did not happen, indicating that pilocarpine attenuated the fever-inducing effect of endotoxin, and thus provides support for existence of a cholinergic anti-inflammatory pathway in sheep. The haematocrit data supported this finding.