Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infection with caprine arthritis encephalitis virus

We have studied the expression of the inducible form of nitric oxide syntha se (iNOS) in joints of goats infected with the caprine arthritis encephalit is virus (CAEV). Nitric oxide generated by iNOS is thought to play an impor tant role in the pathogenesis of various types of arthritis, especially rhe umatoid arthritis (RA) in humans. Surprisingly, iNOS immunoreactivity was f ound only in joints of long-term infected goats with severe clinical arthri tis, whereas-despite the presence of high numbers of inflammatory cells in the synovial tissue-no iNOS immunoreactivity was detected in mildly arthrit ic and in shortterm experimentally infected goats. Most iNOS-positive cells expressed neither MHC class II nor CD68, which suggests that they were fib roblast-like synoviocytes. In situ hybridization studies showed that there was no correlation between iNOS immunoreactivity and detectable virus expre ssion in the joint. In addition, infection of macrophages in vitro-the majo r host cells of CAEV in vivo-did not lead to increased iNOS mRNA expression . In response to stimulation, similar levels of iNOS expression were observ ed in infected and in uninfected macrophages. These findings suggest that t he expression of iNOS is a feature of late-stage chronic arthritis and is n ot involved in the development of the inflammatory lesions. Both the lack o f co-localization of iNOS protein and viral transcripts in the joint and th e finding that CAEV does not stimulate the expression of iNOS in vitro furt her suggest that iNOS is not directly induced by the virus or the anti-vira l immune response in the joint, that it may well, however, be involved in t issue remodelling or scar formation.