The presence of endotoxin activity in cases of experimentally-induced heartwater in sheep

VAN AMSTEL, S. R., OBEREM, P. T., DIDOMENICO, M., KIRKPATRICK, R. D. & MATHEE, JACKIE, 1988. The presence of endotoxin activity in ca . ses of experimentally-induced heartwater in sheep. Onderstepoort Journal of Veterinary Research, 55, 217-220 (1988) The presence of endotoxin was examined in 5 sheep with experimentally-induced heartwater. Two peaks in endotoxin levels were recorded in 4 out of the 5 sheep during the acute stage of the disease. The 1st peak coincided with or occurred shortly after the febrile reactiOn (over 40 •q. The 2nd peak occurred 3-5 days after the 1st, and in 2 sheep this 2nd elevation in endotoxin levels was associated with severe clinical signs (rapid and laboured breathing, cyanosis and recumbency), and 1 of the 2 sheep died on the day of the 2nd elevation. Both endotoxin peaks were of short duration and levels had decreased in the 24-h follow-up samples. INrRODUCTION The discrepancy between the apparently limited mor­ phological cellular changes, including those on an ultra­ structural level, and the severity of the effusions found in the lungs and body cavities led to speculation about the involvement of a toxin in the pathogenesis of heartwater (Neitz, 1968; Pienaar, 1970; Camus & Barre, 1982, citing Jackson & Neitz, 1932; Bezuidenhout, 1982; Pro­ zesky & DuPlessis, 1985). Parker & Neva (1954) found that the intravenous injection of lethal and sublethal doses of Rickettsia prowazekii into mice produced patho­ logical changes similar to those described for bacterial endotoxins. These changes included focal hepatic necro­ sis and haemorrhages in various organs, including the intestine. More recently Amano & Williams (1984) reported on the characterization of lipopolysasccharide (LPS) ex­ tracted from Phase 1 Coxiella burnetii. They found that the chemical composition of LPS, including the lipid A moiety from C. burnetii, differed significantly from that of gram-negative Enterobacteriaceae. Despite this, LPS extracted with hot phenol-water from Phase 1 C. burnetii, showed some biological activi­ ties associated with the endotoxic LPS from gram-nega­ tive Enterobacteriaceae (Amano & Williams, 1984). On the basis of the foregoing it seems feasible that the caus­ ative organism of heartwater (gram-negatively staining rickettsia, Cowdria ruminantium) may also contain a biologically active LPS on its outer membrane. Varia­ tions in the chemical composition of LPS, including the endotoxically active lipid A, also occur in members of the gram-negative Enterobacteriaceae, with resulting dif­ ferences in biological activity (Morrison & Ulevitch, 1978). The biological activities of endotoxin in the body are very diverse and include those changes associated with the pathogenesis of the acute inflammatory reaction. One such reaction of importance is damage to vascular walls with leakage of protein-rich fluid and blood cellular elements. This damage, caused by the direct interaction of endotoxin with endothelial cells, results in such mor­ phological changes as endothelial cell stripping, distor­ tion, vacuolization and absence of endothelial cell nuclei (Morrison & Ulevitch, 1978). In their review on the effects of bacterial endotoxins on host mediation sys­ tems, these authors, however, state that other researchers were unable to demonstrate any evidence of endothelial damage in experimentally-induced endotoxaemia in