AUGMENTED LEVELS OF MACROPHAGE AND TH1 CELL-RELATED CYTOKINE MESSENGER-RNA IN SUBMANDIBULAR GLANDS OF MRL LPR MICE WITH AUTOIMMUNE SIALOADENITIS/

MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop destructive inflam mation of the salivary and lachrymal glands resembling Sjogren's syndr ome (SS), representing an animal model to study this disease. We used in situ hybridization with synthetic radiolabelled oligonucleotide pro bes to examine expression of mRNA encoding pro- and anti-inflammatory cytokines in submandibular glands of 2, 3, 4 and 5-month-old MRL/lpr m ice. Phenotypic composition of submandibular gland infiltrates was eva luated by immunohistochemistry. Cells expressing tumour necrosis facto r-alpha (TNF-alpha), IL-1 beta, IL-6 and IL-12 mRNA were strongly up-r egulated at about the time of onset of sialoadenitis, suggesting a rol e of these cytokines in development of the disease. Interferon-gamma ( IFN-gamma) and cytolysin mRNA-expressing cells were gradually up-regul ated over the disease course up to 5 months of age, the time when sial oadenitis is at its height, favouring a role of these cytokines in pro gression of the disease as well. Low levels of IL-10 and transforming growth factor-beta (TGF-beta) mRNA-expressing cells were observed at 2 , 3 and 3 months of age, and were almost undetectable at 5 months. Max imum levels of CD4(+), CD8(+) and interdigitating/dendritic cells, as well as of MHC class II and MHC class I expression were seen at 3 mont hs, with CD4(+) outnumbering CD8(+) cells. Maximum levels of macrophag es were seen at 4 months of age. These data argue for a major role of the proinflammatory cytokines TNF-alpha, IL-1 beta, IL-6, IL-12, IFN-g amma and cytolysin in initiation and perpetuation of autoimmune sialoa denitis in MRL/lpr mice, probably in conjunction with an insufficiency of the anti-inflammatory cytokines TGF-beta and IL-10.