Immunoregulatory role of interleukin 10 in rheumatoid arthritis.

Abstract

The presence and the role of interleukin 10 (IL-10), a potent cytokine synthesis inhibitory factor and antiinflammatory cytokine, were investigated in rheumatoid arthritis (RA). The expression of both mRNA and protein for IL-10 could be demonstrated in RA and osteoarthritis (OA) joints. Human IL-10 mRNA could be demonstrated by polymerase chain reaction amplification of cDNA made by reverse transcription of total RNA extracted directly from synovial tissue in five out of five RA and four out of five OA patients. IL-10 protein was demonstrated by specific immunoassay and immunohistology. IL-10 protein was spontaneously produced in all 11 RA and 17 OA synovial membrane cultures investigated, and this production was sustained for up to 5 d in culture in the absence of any extrinsic stimulation. IL-10 protein could also be detected by immunohistology in all five RA and four OA synovial membrane biopsies investigated, but not three normal synovial membranes. Immunohistology revealed that the IL-10 was localized to the synovial membrane lining layer and mononuclear cell aggregates. Immunofluorescence double staining revealed that the sources of IL-10 were monocytes in the lining layer, and T cells in the mononuclear cell aggregates. We found evidence that the IL-10 expression was functionally relevant, as neutralization of endogenously produced IL-10 in the RA synovial membrane cultures resulted in a two- to threefold increase in the protein levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-1 beta, although IL-6 and IL-8 levels were not affected. The addition of exogenous recombinant IL-10 to the RA synovial membrane cultures resulted in a two- to threefold decrease in the levels of TNF-alpha and IL-1 beta. IL-8 levels were reduced by day 5; however, IL-6 levels were not affected by exogenous IL-10. Neutralization of the endogenous IL-10 in two out of seven RA synovial membrane cultures resulted in the expression of detectable levels of interferon gamma (561-1,050 pg/ml). Taken together, the above findings suggest that IL-10 is spontaneously produced in RA and OA and is an important immunoregulatory component in the cytokine network of RA, regulating monocyte and in some cases T cell cytokine production.

Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: A two‐year prospective study (the DAMAGE study cohort)

“…Many studies suggest that IL-10 acts as an antiinflammatory cytokine in RA (28,29). These studies were performed in animal models or in vitro assays and gave no indication that IL-10 mediated bone resorption, either directly or indirectly.…”

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

“…IL-10 has a number of immunoregulatory effects. It inhibits the synthesis of proinflammatory cytokines, such as TNF-a, IL-1 and GM-CSF, by human monocytes stimulated with LPS [26], and neutralization of IL-10 in synovial cell cultures results in enhanced IL-1 and TNF-a production [27]. IL-10 also interferes with the production of interferon-g (IFN-g) IgG2bIF, immunoglobulin G2b-inducing factor; IL, interleukin; TGF-b, transforming growth factor-b; TNF-a, tumour necrosis factor-a.…”

Interleukin‐8, Interleukin‐10, Intercellular Adhesion Molecule‐1 and Vascular Cell Adhesion Molecule‐1 Expression Levels are Higher in Synovial Tissue from Patients with Rheumatoid Arthritis than in Osteoarthritis

“…Thus, T-cell and neutrophil chemotaxis, a crucial process for leucocyte accumulation, is predominantly induced by interleukin (IL)-8 [6][7][8][9][10]. Other cytokines, such as IL-1, IL-6, tumour necrosis factor-␣ (TNF-␣), granulocyte and monocyte colony-stimulating factor (GM-CSF), transforming growth factor-␤ (TGF-␤) and IL-10, have also been detected in the RA joint [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. Overexpression of IL-1␣, IL-1␤, IL-6, TNF-␣, GM-CSF and epidermal growth factor (EGF) has been described in OA synovium [4,[24][25][26].…”