Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren's syndrome and correlate with the clinical manifestations of the disease.

OBJECTIVES To determine whether plasma interleukin-6 (IL-6) and G/C base exchange polymorphism at position -174 of the IL6 gene have an effect on the clinical manifestations of primary Sjögren's syndrome (pSS). METHODS Levels of circulating IL-6 protein and polymorphism of the IL6 gene were analysed in 66 patients with pSS and in 400 healthy subjects. These data were studied in relation to clinical data on the pSS patients. RESULTS Plasma IL-6 was elevated in pSS patients compared with healthy controls. pSS patients with coeliac disease, pulmonary fibrosis or alveolitis or peripheral nervous system symptoms had significantly higher IL-6 levels than patients without these manifestations. IL-6 levels increased in parallel with the histological grade of minor salivary gland biopsy and the number of pSS criteria fulfilled. IL6 allele frequencies were similar in patients and normal subjects. Plasma IL-6 levels were regulated by the IL6 genotype in pSS patients. CONCLUSIONS The G/C polymorphism of the IL6 gene does not predispose patients to pSS, but the circulating IL-6 concentration is related to specific manifestations of the disease and the levels of IL-6 are regulated by the IL6 promoter polymorphism in pSS.

[1]  A. Pasternack,et al.  The occurrence of renal involvement in primary Sjögren's syndrome: a study of 78 patients. , 1999, Rheumatology.

[2]  P. Fraser,et al.  Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression , 1999, Genes and Immunity.

[3]  Zhu,et al.  Local effects of recombinant rat interleukin‐6 on the peripheral nervous system , 1999, Immunology.

[4]  Mills,et al.  T cell proliferation, MHC class II restriction and cytokine products of gliadin‐stimulated peripheral blood mononuclear cells (PBMC) , 1999, Clinical and experimental immunology.

[5]  R. Jonsson,et al.  Increased Frequency of Cells Secreting Interleukin‐6 and Interleukin‐10 in Peripheral Blood of Patients with Primary Sjögren's Syndrome , 1999, Scandinavian journal of immunology.

[6]  Hongzhen Hu,et al.  IL-1β and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system , 1999 .

[7]  M. Mäki,et al.  Celiac disease and markers of celiac disease latency in patients with primary Sjögren's syndrome , 1999, American Journal of Gastroenterology.

[8]  J. Harley,et al.  Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. , 1999, Arthritis and rheumatism.

[9]  M. Yaron,et al.  Elevated tear interleukin-6 levels in patients with Sjögren syndrome. , 1998, Ophthalmology.

[10]  J S Yudkin,et al.  The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. , 1998, The Journal of clinical investigation.

[11]  S. Rose-John,et al.  Sympathetic neurons can produce and respond to interleukin 6. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Fujimoto,et al.  Serum levels of interleukin 6 (IL-6), oncostatin M, soluble IL-6 receptor, and soluble gp130 in patients with systemic sclerosis. , 1998, The Journal of rheumatology.

[13]  P. Fox,et al.  Salivary and serum interleukin 6 in primary Sjögren's syndrome. , 1997, The Journal of rheumatology.

[14]  P. Roux‐Lombard,et al.  IL‐1 receptor antagonist in saliva; characterization in normal saliva and reduced concentration in Sjo¨gren's syndrome (SS) , 1996, Clinical and experimental immunology.

[15]  E. Fireman,et al.  Effect of IL-6 on alveolar fibroblast proliferation in interstitial lung diseases. , 1996, Clinical immunology and immunopathology.

[16]  K. Asmussen,et al.  A new model for classification of disease manifestations in primary Sjögren's syndrome: evaluation in a retrospective long‐term study , 1996, Journal of internal medicine.

[17]  R. Scofield.  Autoimmune thyroid disease in systemic lupus erythematosus and Sjögren's syndrome. , 1996, Clinical and experimental rheumatology.

[18]  K. Lundin,et al.  Gluten activation of peripheral blood T cells induces a Th0‐like cytokine pattern in both coeliac patients and controls , 1996, Clinical and experimental immunology.

[19]  Y. Kaneda,et al.  A histologically distinctive interstitial pneumonia induced by overexpression of the interleukin 6, transforming growth factor beta 1, or platelet-derived growth factor B gene. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[20]  J. Alcocer-Varela,et al.  In vivo production of interleukin-10 by non-T cells in rheumatoid arthritis, Sjögren's syndrome, and systemic lupus erythematosus. A potential mechanism of B lymphocyte hyperactivity and autoimmunity. , 1994, Arthritis and rheumatism.

[21]  P. Ciclitira,et al.  Raised pro-inflammatory cytokines interleukin 6 and tumour necrosis factor alpha in coeliac disease mucosa detected by immunohistochemistry. , 1994, Gut.

[22]  H. Moutsopoulos,et al.  Sjögren's syndrome: autoimmune epithelitis. , 1994, Bailliere's best practice & research. Clinical rheumatology.

[23]  C. Pease,et al.  Serological and immunogenetic markers of extraglandular primary Sjögren's syndrome. , 1993, British journal of rheumatology.

[24]  A. Teppo,et al.  Immunoreactive interleukin‐6 in serum of patients with B‐lymphoproliferative diseases , 1992, Journal of internal medicine.

[25]  T. Kishimoto,et al.  Interleukin-6 and its receptor in autoimmunity. , 1992, Journal of autoimmunity.

[26]  W. Dick,et al.  Primary Sjögren's syndrome in north east England--a longitudinal study. , 1991, British journal of rheumatology.

[27]  Z. Han,et al.  Megakaryocytopoiesis: characterization and regulation in normal and pathologic states. , 1991, International journal of hematology.

[28]  P. Maddison.  Overlap syndromes and mixed connective tissue disease , 1990, Current opinion in rheumatology.

[29]  J. Hoofnagle,et al.  Sjögren's syndrome in patients with primary biliary cirrhosis , 1990, Hepatology.

[30]  T. Hirano,et al.  In vivo effects of recombinant human interleukin-6 in primates: stimulated production of platelets. , 1990, Blood.

[31]  P. Youinou,et al.  New developments in Sjögren's syndrome , 1989, Current opinion in rheumatology.

[32]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[33]  E. Rosenow,et al.  Pulmonary manifestations of Sjögren's syndrome. , 1976, Chest.

[34]  D. Chisholm,et al.  Labial salivary gland biopsy in Sjögren's disease , 1968, Journal of clinical pathology.

[35]  D. Klinman,et al.  Altered frequency of type 1 cytokine secreting cells in the peripheral blood of patients with primary Sjögren's syndrome. , 1998, The Journal of rheumatology.

[36]  T. Mimori,et al.  Clinical significance of antibodies to native or denatured 60-kd or 52-kd Ro/SS-A proteins in Sjögren's syndrome. , 1994, Arthritis and rheumatism.