IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis.

Abstract

T lymphocytes are a major component of the inflammatory infiltrate in rheumatoid synovitis, but their exact role in the disease process is not understood. Functional activities of synovial T cells were examined by adoptive transfer experiments in human synovium-SCID mouse chimeras. Adoptive transfer of tissue-derived autologous CD8+ T cells induced a marked reduction in the activity of lesional T cells and macrophages. Injection of CD8+, but not CD4+, T cells decreased the production of tissue IFN-gamma, IL-1beta, and TNF-alpha by >90%. The down-regulatory effect of adoptively transferred CD8+ T cells was not associated with depletion of synovial CD3+ T cells or synovial CD68+ macrophages, and it could be blocked by Abs against IL-16, a CD8+ T cell-derived cytokine. In the synovial tissue, CD8+ T cells were the major source of IL-16, a natural ligand of the CD4 molecule that can anergize CD4-expressing cells. The anti-inflammatory activity of IL-16 in rheumatoid synovitis was confirmed by treating synovium-SCID mouse chimeras with IL-16. Therapy for 14 days with recombinant human IL-16 significantly inhibited the production of IFN-gamma, IL-1beta, and TNF-alpha in the synovium. We propose that tissue-infiltrating CD8+ T cells in rheumatoid synovitis have anti-inflammatory activity that is at least partially mediated by the release of IL-16. Spontaneous production of IL-16 in synovial lesions impairs the functional activity of CD4+ T cells but is insufficient to completely abrogate their stimulation. Supplemental therapy with IL-16 may be a novel and effective treatment for rheumatoid arthritis.

• Authors: P A Klimiuk, J J Goronzy, C M Weyand
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 162 Issue 7 Pg. 4293-9 (Apr 01 1999) ISSN: 0022-1767 [Print] United States
• PMID: 10201961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Interleukin-16

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, antagonists & inhibitors, pharmacology)
• Arthritis, Rheumatoid (immunology, pathology, therapy)
• CD8-Positive T-Lymphocytes (immunology, metabolism, pathology)
• Cells, Cultured
• Chronic Disease
• Down-Regulation (immunology)
• Humans
• Injections, Intraperitoneal
• Interleukin-16 (administration & dosage, antagonists & inhibitors, biosynthesis, physiology)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Synovial Membrane (immunology, metabolism, pathology)
• Synovitis (immunology, pathology, therapy)