CYTOKINE MESSENGER-RNA EXPRESSION IN SALIVARY-GLAND BIOPSIES OF SJOGRENS-SYNDROME

Sjogren's syndrome is a human autoimmune disease characterized by lymp hocytic infiltration of salivary and lacrimal glands, hypergammaglobul inemia, and specific autoantibodies. The accessibility of the salivary gland to biopsy provides an opportunity to study cytokine mRNA expres sion at the site of organ-specific immune damage. Using reverse transc riptase and a quantitative PCR to measure cytokine mRNA, we found Sjog ren's syndrome: 1) salivary gland CD4(+) T cells produce over 40-fold more IL-2, IFN-gamma, and IL-10 mRNA than peripheral blood CD4(+) T ce lls from the same patient or from normal controls; 2) salivary gland C D4(+) T cells produced little IL-4 and IL-5 mRNA immediately after elu tion from the salivary gland, although these mRNAs could be induced by mitogen stimulation of Sjogren's syndrome salivary gland lymphocytes in vitro; 3) salivary gland epithelial cells produced over 40-fold mor e IL-1 alpha, IL-6, and TNF-alpha mRNA than epithelial cells from indi viduals with histologically normal salivary glands. Increased levels o f IL-1 alpha, IL-6, IL-10, TNF-alpha, and IFN-gamma cytokines were fou nd by ELISA assay in the saliva of Sjogren's syndrome patients, indica ting that the elevated mRNA levels detected in their glandular tissue by PCR correlate with local protein synthesis. Our results demonstrate that CD4(+) cells in the salivary glands of Sjogren's syndrome patien ts exhibit mRNA expression that is distinct from previously described Th1 and Th2 lymphocytes in mice or cytokines reported in other human a utoimmune or allergic diseases. Also, we found that salivary gland epi thelial cells may participate in the pathogenesis of Sjogren's syndrom e biopsy by producing cytokines (IL-1 alpha, IL-6, and TNF-alpha).