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Endogenous mediators of the acute-phase reaction. I. Rabbit granulocytic pyrogen and its chromatographic subfractions.

LP, a saline extract of exudate-derived rabbit granulocytes, shown to be free of endotoxin contamination by sensitive LAL assay, can elicit brisk acute-phase responses in the rabbit. Following a single large intravenous dose of LP (875 mce) there is a brisk fall in serum iron at 8 hr and marked elevations in concentrations of CxRP, haptoglobin, fibrinogen, and ceruloplasmin and a lesser rise in sialic acid in the blood at 24 hr, which return toward baseline to varying degrees by 48 hr. When the crude LP solution is fractionated by column chromatography on Sephadex G75, all detectable acute-phase mediating activity elutes in a fraction (pool C) which contains all the pyrogenic activity and about 15% of the total eluted protein. Within the limitations of the methods employed, the acute phase stimulating activity and the pyrogenic activity of LP preparations appear to be closely linked.

Animals↗

Immunochemical relationship of three antigens purified from Pasteurella multocida strain P-1059.

Three antigens were prepared from a type-3 avian strain of Pasteurella multocida, and their chemical and immunologic characteristics were studied. An antigen, designated 2.5S, was extracted with 2.5% NaCl solution and purified by chromatography. Lipopolysaccharide (LPS) was extracted with phenol-water, and a third antigen, designated FS, was extracted in 0.3% formalin solution containing 0.85% NaCl and purified by differential centrifugation. The 2.5S and the FS antigens consisted of 40% protein and 15% carbohydrate, whereas LPS did not contain a substantial amount of protein. A major protein component with a molecular weight of 44,000 was detected in the 2.5S antigen, as well as in the FS antigen. Of the 3 antigens, LPS had the highest activity in mouse lethality and Limulus lysate tests. Antigenic cross-reactions among the 3 antigens were demonstrated by immunodiffusion tests. The 2.5S antigen was indistinguishable from the FS antigen, as both antigens contained the LPS component of approximately 45%. Treatments with various reagents indicated that the 2.5S and FS antigens contained at least 2 antigenic determinants. The first was a heat-stable protein sensitive to protease or phenol-water, and the second was a periodate-sensitive carbohydrate, which was a major antigenic determinant on the LPS antigen.

Antigens, Bacterial↗

[Determination of endotoxin in inflammatory rheumatic diseases--the effect of nonsteroidal anti-inflammatory agents on intestinal permeability].

We measured the amount of plasma endotoxin in 95 patients with inflammatory rheumatic diseases (42 with ankylosing spondylitis; 12 with possible ankylosing spondylitis; 41 with rheumatoid arthritis) and in 16 patients with Crohn's disease with a quantitative Limulus assay. Significantly increased mean values were found in inflammatory rheumatic diseases and in Crohn's disease. Between 31% and 50% of the patients had endotoxin values higher than 10 pg/ml--none of the controls had such values. Patients on regular treatment with NSAIDS had higher amounts of endotoxin again. From our results we discuss an intestinal involvement in inflammatory rheumatic diseases. An inflammation of the gut with an increased permeability seems to be responsible for the raised plasma endotoxin levels compared to healthy controls. NSAIDs probably contribute to the increased permeability of the gut.

Adult↗

Endotoxaemia in racehorses following exertion.

Endotoxins (lipopolysaccharides-LPS) and anti-endotoxin IgG antibodies were measured in racehorses before and after races of 1,000, 2,000 and 2,800 m. Results show that the mean plasma concentration of endotoxin increased significantly (p less than 0.02) while the anti-LPS IgG concentration decreased significantly (p less than 0.005) in all horses following the races. Pre-race and post-race anti-LPS IgG levels in racing-fit racehorses were significantly higher than in untrained horses (p less than 0.05). The possibility therefore exists that training-induced stress leads to leakage of LPS into the systemic circulation which results in self-immunisation against LPS. The effects of plasma LPS and anti-LPS IgG concentrations on performance of racehorses require further studies.

Animals↗