INTERFERON-GAMMA IMMUNOREACTIVITY IN IRIS NERVE-FIBERS DURING ENDOTOXIN-INDUCED UVEITIS IN THE RAT

Aims-Previous studies have implied that interferon gamma (IFN-gamma) i s involved in the pathogenesis of endotoxin induced uveitis (EIU) in t he rat. This study investigated the source of IFN-gamma in the iris du ring EIU. Methods-Whole mounts of iris were isolated from Lewis rats b efore and at different times (from 4 hours to 14 days) after foot pad injection of 200 mu g Salmonella typhimurium lipopolysaccharide (LPS). Immunohistological analysis was performed using monoclonal antibodies (mAbs) specific to rat IFN-gamma (DB12 and DB13). mAbs specific to mo nocytes, macrophages, and dendritic cells and MHC class II were used t o asses the inflammatory response in the eye (ED-1, ED-2, and OX-6). A n antibody specific to neurofilaments (2H3) was used to stain nerve fi bres in the normal iris. Results-LPS administration induced acute intr aocular inflammation, characterised by a massive infiltration of monoc ytes/macrophages and increased numbers of MHC class II positive cells in the iris. IFN-gamma immunoreactive cells were not detected in iris whole mounts of control rats. Strikingly, IFN-gamma immunoreactivity w as found in fibres from 4 hours until 10 days after LPS injection, wit h the most intense staining at 48-72 hours. Other DB12 or DB13 positiv e cells were not detected in the iris. The pattern of DB12 and DB13 st aining in the inflamed iris was similar to the 2H3 staining of neurons in the iris of control rats. Conclusion-These results show that syste mic LPS administration induces IFN-gamma immunoreactivity in iris fibr es and suggest that iris nerve fibres may be a source of IFN-gamma dur ing EIU. The IFN-gamma immunoreactive material in the iris nerve fibre s may be identical to neuronal IFN-gamma.