ABSTRACT
6-Sulfanilamidoindazole (6SAI) induces selflimiting arthritis in rats. Since close relationships exist between arthritis and endotoxin, four experiments were conducted to clarify the relationship between endotoxin and 6SAI-induced arthritis. Endotoxin levels in the plasma from the abdominal aorta and portal vein from rats that had 6SAI (500 mg/kg) administered orally for up to 7 days remained within the control values at day 1 and day 3, and were significantly elevated at day 7. Endotoxin levels in the synovial fluid from the same rats showed no significant change. Ankle swelling and redness in rats treated 11 consecutive days with 6SAI did not ameliorate when coadministered with an anti-endotoxin agent, polymyxin B sulfate. Histopathological examination on the ankles of rats treated orally with non-arthiritogenic sulfonamides including sulfonamide, sulfamethoxazole and sulfadimethoxin (250 and 500 mg/kg/day, each compound) for 2 weeks demonstrated no inflammatory changes, while hyperplasia/hypertrophy of thyroid epithelial cells were frequently observed. When histopathological changes in the ankles from rats coadministered with 6SAI and lipopolysaccharide (LPS, Escherihia coli O55:B5, 50 microg/kg, i.v.) were compared with those in rats treated with 6SAI or LPS alone, the ankles from the 6SAI+LPS treated animals had marked edematous inflammation in the synovium and surrounding connective tissues, whereas the LPS-group had only mild focal infiltration of polymorphonuclear leukocytes in the synovium and the 6SAI-group showed no apparent changes. These results suggest that endotoxin is not a direct cause but a possible acceralating factor of 6SAI-induced arthritis, and that the effects of 6SAI on gut bacteria is not related with the pathogenesis of this model.
Subject(s)
Arthritis, Experimental/blood , Endotoxins/blood , Administration, Oral , Animals , Arthritis, Experimental/chemically induced , Arthritis, Experimental/pathology , Disease Models, Animal , Drug Antagonism , Escherichia coli , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/pharmacology , Male , Polymyxin B/pharmacology , Rats , Rats, Inbred Strains , Serositis/blood , Serositis/chemically induced , Serositis/parasitology , Sulfanilamides/toxicity , Synovial Fluid/drug effects , Synovial Fluid/metabolismABSTRACT
CONTEXT: Enterocytozoon bieneusi is the most frequent microsporidian parasite of human patients with acquired immunodeficiency syndrome and is a significant cause of diarrhea and wasting. Recently, this organism has also been recognized as a spontaneous infection of several species of captive macaques. As in humans, E bieneusi frequently causes enteropathy and cholangiohepatitis in immunodeficient simian immunodeficiency virus (SIV)-infected macaques. OBJECTIVE: To examine E bieneusi as an etiologic agent of nonsuppurative proliferative serositis in immunodeficient rhesus macaques (Macaca mulatta). DESIGN: Retrospective analysis of necropsy material obtained from immunodeficient SIV-infected rhesus macaques. RESULTS: Examination of SIV-infected rhesus macaques (n = 225) revealed E bieneusi proliferative serositis in 7 of 16 cases of peritonitis of unknown origin. The organism could be identified by in situ hybridization and polymerase chain reaction in sections of pleura and peritoneum obtained at necropsy. Serositis was always accompanied by moderate-to-severe infection of the alimentary tract, and morphologic evidence suggested dissemination through efferent lymphatics. Colabeling experiments revealed most infected cells to be cytokeratin positive and less frequently positive for the macrophage marker CD68. Sequencing of a 607-base pair segment of the small subunit ribosomal gene revealed 100% identity to sequences obtained from rhesus macaques (Genbank accession AF023245) and human patients (Genbank accession AF024657 and L16868). CONCLUSIONS: These findings indicate that E bieneusi disseminates in immunodeficient macaques and may be a cause of peritonitis in the immunocompromised host.
