Human interleukin 1 mediates cartilage matrix degradation.

Area of Science:

• Immunology
• Biochemistry
• Rheumatology

Background:

• Human monocyte factors are known to mediate cartilage matrix degradation through chondrocyte activation.
• Interleukin 1 (IL-1) is a key cytokine implicated in inflammatory processes.

Purpose of the Study:

• To investigate the cartilage matrix-degrading activity of partially purified human monocyte-derived Interleukin 1 (IL-1).
• To determine if IL-1 is responsible for the matrix degradation observed in chronic inflammatory arthritides.

Main Methods:

• Human monocyte or blood mononuclear cell culture supernatants were purified using various chromatography techniques (phenyl-Sepharose, gel filtration, isoelectric focusing, chromatofocusing).
• Purified fractions were tested for Interleukin 1 (IL-1) activity using mouse thymocyte proliferation assays.
• The same fractions were assessed for their ability to induce matrix macromolecule release from bovine cartilage explants in organ culture.

Main Results:

• The cartilage matrix-degrading activity and the thymocyte proliferating activity (IL-1 activity) exhibited identical purification profiles based on molecular size, hydrophobicity, and net charge.
• Thermal denaturation studies could not differentiate between the thymocyte proliferating and matrix-degrading activities.
• These results strongly indicate that IL-1 possesses matrix-degrading properties.

Conclusions:

• Interleukin 1 (IL-1) directly mediates cartilage matrix degradation by activating resident chondrocytes.
• IL-1 found in inflammatory synovial fluids likely plays a significant role in cartilage damage in chronic inflammatory arthritides, such as rheumatoid arthritis.