Specific Antibodies to Om-89 Can Account for its Clinical Anti-Inflammatory Properties

The glycoprotein rich extract of E.coli, OM-89, has immunomodulatory properties and is used in the treatment of rheumatoid arthritis. One property ascribed to OM-89 is polyclonal B cell activation, however, less clear is whether administration of the drug results in the appearance of specific B-cell responses. Immunoprecipitation was used to demonstrate that OM-89 reactive antibody compexes could be formed in serum following oral (40mg/kg) or parenteral administration of OM-89. ELISAs were developed to measure OM-89 specific antibody isotypes (IgM, IgG1, IgG2a, IgG2b and IgG2c) in serum from orally dosed rats (4, 40 and 400mg/kg, 3 times a week for 6 weeks). A significant (p<0.05) increase in OM-89 specific IgG2a was observed at a dose of 40mg/kg, a dose shown previously to be efficacious in animal models of inflammation. These animals had significant elevations in IgG2a anti-GroEL (p<0.05) and anti-DnaK (p<0.05), major immunogenic epitopes in the drug. The possibility that these antibodies could be protective against chronic inflammation was investigated by examining the effect of serum transfer from OM-89 sensitised rabbits on granuloma weight in the cotton pellet model of chronic inflammation in rats. Serum from immune animals reduced granuloma weight by 22% (p<0.05) compared to untreated controls and by 33% (p<0.001) compared to controls dosed with the pre-immune serum. These results suggest that the induction of protective/blocking antibodies represents one mechanism in the therapeutic action of OM-89.