The influence of experimentally-induced endotoxaemia on clinical variables and markers of systemic inflammation in donkeys (Equus asinus)

Abstract

In view of the frequent involvement of endotoxins in the pathogenesis of equine diseases, the present study set out to gain preliminary insight into the challenge caused by lipopolysaccharide (LPS) exposure in donkeys and into the responses of animals to LPS challenge. To the best of our knowledge, this is the first study to determine the susceptibility and response of donkeys to LPS administration and the first to describe the extent to which donkeys can tolerate a state of endotoxaemia. For this purpose, 18 clinically healthy, native breed donkeys were randomly allocated into three groups of equal size. The first and second groups received E. coli O55:B5 endotoxin at a dose rate of 20 ng/kg (Low dose group), and 5.0 µg/kg (High dose group), respectively, after dilution in 500 ml of 0.9% normal saline, while the third group (Control) received 500 ml of 0.9% isotonic saline solution. Blood samples were drawn from each animal before exposure to LPS and hourly for 6 h subsequently to measure the circulating levels of inflammatory cytokines as well as the cellular response. All animals were clinically monitored throughout the study period. Following LPS exposure, donkeys in both treated groups had quite different temporal patterns of clinical manifestations. The high dose of LPS yielded a statistically significant (P < 0.001 and P < 0.001, respectively) increase in heart rate, and respiratory rate, as well as hypothermia and poor outcome compared with animals receiving the low dose. The severity of colic was, in general, mild in donkeys receiving the low dose of LPS, while the signs were overt in those receiving the high dose. Donkeys of both treated groups exhibited marked cellular alterations and up-regulation of tumour necrosis factor alpha, interleukin (IL)-12 and IL-10 with a marginal increase in the values of serum amyloid A compared with controls (P < 0.05). The results described herein demonstrate that donkeys can respond to even a physiological dose of E. coli O55:B5 endotoxin, while a high dose can elicit overt clinical alterations and marked inflammatory responses. Further studies with an extended follow-up time are needed to verify and generalise the obtained findings and to evaluate novel medications to minimise the deleterious consequences of endotoxaemia in equine patients.