Immunoregulatory role of interleukin 10 in rheumatoid arthritis

Peter D. Katsikis, Cong-Qiu Chu, Brennan Fionula M, Ravinder N. Maini, Marc Feldmann

Research output: Contribution to journalArticle

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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 α (TNF-α) and IL-1β, 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-α and IL-1β. 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 γ (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.

Original languageEnglish (US)
Pages (from-to)1517-1527
Number of pages11
JournalJournal of Experimental Medicine
Volume179
Issue number5
StatePublished - May 1 1994
Externally publishedYes

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Interleukin-10
Rheumatoid Arthritis
Synovial Membrane
Osteoarthritis
Cytokines
Proteins
Interleukin-8
Interleukin-1
Monocytes
Interleukin-6
Tumor Necrosis Factor-alpha
T-Lymphocytes
Messenger RNA
Immunoassay
Interferons
Reverse Transcription
Fluorescent Antibody Technique
Anti-Inflammatory Agents
Complementary DNA
Joints

ASJC Scopus subject areas

  • Immunology

Cite this

Katsikis, P. D., Chu, C-Q., Fionula M, B., Maini, R. N., & Feldmann, M. (1994). Immunoregulatory role of interleukin 10 in rheumatoid arthritis. Journal of Experimental Medicine, 179(5), 1517-1527.

Immunoregulatory role of interleukin 10 in rheumatoid arthritis. / Katsikis, Peter D.; Chu, Cong-Qiu; Fionula M, Brennan; Maini, Ravinder N.; Feldmann, Marc.

In: Journal of Experimental Medicine, Vol. 179, No. 5, 01.05.1994, p. 1517-1527.

Research output: Contribution to journalArticle

Katsikis, PD, Chu, C-Q, Fionula M, B, Maini, RN & Feldmann, M 1994, 'Immunoregulatory role of interleukin 10 in rheumatoid arthritis', Journal of Experimental Medicine, vol. 179, no. 5, pp. 1517-1527.
Katsikis PD, Chu C-Q, Fionula M B, Maini RN, Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. Journal of Experimental Medicine. 1994 May 1;179(5):1517-1527.
Katsikis, Peter D. ; Chu, Cong-Qiu ; Fionula M, Brennan ; Maini, Ravinder N. ; Feldmann, Marc. / Immunoregulatory role of interleukin 10 in rheumatoid arthritis. In: Journal of Experimental Medicine. 1994 ; Vol. 179, No. 5. pp. 1517-1527.
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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 α (TNF-α) and IL-1β, 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-α and IL-1β. 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 γ (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.",
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