Apolipoprotein A-I infiltration in rheumatoid arthritis synovial tissue: a control mechanism of cytokine production?

Arthritis Research & Therapy

Barry Bresnihan¹  Martina Gogarty¹  Oliver FitzGerald¹  Jean-Michel Dayer²  Danielle Burger² 

[1] Department of Rheumatology, St Vincents University Hospital, Dublin, Ireland

[2] Service of Immunology and Allergy, Faculty of Medicine, Geneva, Switzerland

关键词: synovium;    rheumatoid arthritis;    inflammation;    cytokines;    apolipoprotein A-I;   

Others  :  1101190
DOI  :  10.1186/ar1443

 received in 2004-06-22, accepted in 2004-08-19,  发布年份 2004

【 摘 要 】

The production of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) by monocytes is strongly induced by direct contact with stimulated T lymphocytes, and this mechanism may be critical in the pathogenesis of rheumatoid arthritis (RA). Apolipoprotein A-I (apoA-I) blocks contact-mediated activation of monocytes, causing inhibition of TNF-α and IL-1β production. This study examined the hypothesis that apoA-I may have a regulatory role at sites of macrophage activation by T lymphocytes in inflamed RA synovial tissue. Synovial tissue samples were obtained after arthroscopy from patients with early untreated RA or treated RA and from normal subjects. As determined by immunohistochemistry, apoA-I was consistently present in inflamed synovial tissue that contained infiltrating T cells and macrophages, but it was absent from noninflamed tissue samples obtained from treated patients and from normal subjects. ApoA-I staining was abundant in the perivascular areas and extended in a halo-like pattern to the surrounding cellular infiltrate. C-reactive protein and serum amyloid A were not detected in the same perivascular areas of inflamed tissues. The abundant presence of apoA-I in the perivascular cellular infiltrates of inflamed RA synovial tissue extends the observations in vitro that showed that apoA-I can modify contact-mediated macrophage production of TNF-α and IL-1β. ApoA-I was not present in synovium from patients in apparent remission, suggesting that it has a specific role during phases of disease activity. These findings support the suggestion that the biologic properties of apoA-I, about which knowledge is newly emerging, include anti-inflammatory activities and therefore have important implications for the treatment of chronic inflammatory diseases.

【 授权许可】

   
2004 Bresnihan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Firestein GS, Zvaifler NJ: How important are T cells in chronic rheumatoid synovitis?: II. T cell-independent mechanisms from beginning to end. Arthritis Rheum 2002, 46:298-308.
• [2]Burger D: Cell contact-mediated signaling of monocytes by stimulated T cells: a major pathway for cytokine induction. Eur Cytokine Netw 2000, 11:346-353.
• [3]Feldmann M, Maini RN: Anti TNF-alpha therapy of rheumatoid arthritis: What have we learned? Annu Rev Immunol 2001, 19:163-196.
• [4]Dayer JM, Feige U, Edwards CK III, Burger D: Anti-interleukin-1 therapy in rheumatic diseases. Curr Opin Rheumatol 2001, 13:170-176.
• [5]Hyka N, Dayer JM, Modoux C, Kohno T, Edwards CK III, Roux-Lombard P, Burger D: Apolipoprotein A-I inhibits the production of interleukin-1beta and tumor necrosis factor-alpha by blocking contact-mediated activation of monocytes by T lymphocytes. Blood 2001, 97:2381-2389.
• [6]Park YB, Lee SK, Lee WK, Suh CH, Lee CW, Lee CH, Song CH, Lee J: Lipid profiles in untreated patients with rheumatoid arthritis. J Rheumatol 1999, 26:1701-1704.
• [7]Lakatos J, Harsagyi A: Serum total, HDL, LDL cholesterol, and triglyceride levels in patients with rheumatoid arthritis. Clin Biochem 1988, 21:93-96.
• [8]Doherty NS, Littman BH, Reilly K, Swindell AC, Buss JM, Anderson NL: Analysis of changes in acute-phase plasma proteins in an acute inflammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 1998, 19:355-363.
• [9]Ananth L, Prete PE, Kashyap ML: Apolipoproteins A-I and B and cholesterol in synovial fluid of patients with rheumatoid arthritis. Metabolism 1993, 42:803-806.
• [10]O'Hara R, Murphy EP, Whitehead AS, Fitzgerald O, Bresnihan B: Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue. Arthritis Res 2000, 2:142-144. BioMed Central Full Text
• [11]Coetzee GA, Strachan AF, van der Westhuyzen DR, Hoppe HC, Jeenah MS, de Beer FC: Serum amyloid A-containing human high density lipoprotein 3. Density, size, and apolipoprotein composition. J Biol Chem 1986, 261:9644-9651.
• [12]Weyand CM, Braun A, Takemura S, Goronzy JJ: Lymphoid microstructures in rheumatoid synovitis. Curr Dir Autoimmun 2001, 3:168-187.
• [13]Patel H, Fellowes R, Coade S, Woo P: Human serum amyloid A has cytokine-like properties. Scand J Immunol 1998, 48:410-418.
• [14]Tselepis AD, Elisaf M, Besis S, Karabina SA, Chapman MJ, Siamopoulou A: Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity. Arthritis Rheum 1999, 42:373-383.
• [15]Tak PP, Smeets TJM, Daha MR, Kluin PM, Meijers KAE, Brand R, Meinders AE, Breedveld FC: Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum 1997, 40:217-225.