Evidence for Endotoxin as a Causative Factor for Leptospiral Uveitis in Humans

Abstract

To understand the pathogenic mechanism of leptospiral uveitis by determining the profile of infiltrating cells, the levels of cytokines, and the causative factor in aqueous humor (AH). AH and blood samples were collected from 22 patients with leptospiral uveitis that was confirmed by microscopic agglutination test (MAT). Nine patients with Behçet's uveitis, 10 with phacolytic uveitis, and 13 with age-related cataract were included as control subjects. A cytometric bead array was used to estimate human inflammatory and Th1/Th2 cytokines. The level of endotoxin in AH was estimated by limulus amebocyte lysate (LAL) test and by dot blot analysis using a leptospiral serovar lipopolysaccharide (LPS)-specific monoclonal antibody. Except for one patient with leptospiral uveitis, AH from all other patients and control subjects was negative for Gram-negative bacterial endotoxin by LAL test. However, a significant level of serovar Copenhageni LPS was observed in AH of patients with leptospiral uveitis seropositive for the same serovar by MAT, in contrast to its absence in all control subjects. A selective infiltration of neutrophils as well as a significant increase in the levels of protein and cytokines IL-12p70, TNF, IL-6, IL-8, and IL-10 was observed in AH of patients with leptospiral uveitis. Phacolytic uveitis was associated with a high proportion of activated macrophages and increased levels of IL-6 and IL-8, whereas Behçet's uveitis was associated with a predominant infiltration of neutrophils and increased levels of IFN-gamma. The results demonstrate the presence of serovar-specific LPS in AH, and thus it is likely that endotoxin is a causative factor in leptospiral uveitis.