IL-4 inhibits growth factor-stimulated rheumatoid synoviocyte proliferation by blocking the early phases of the cell cycle

• Published in: The Journal of immunology (1950) Vol. 151; no. 9; pp. 4908 - 4917
• Main Authors: Dechanet, J, Briolay, J, Rissoan, MC, Chomarat, P, Galizzi, JP, Banchereau, J, Miossec, P
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01.11.1993; American Association of Immunologists
• Subjects: Arthritis, Rheumatoid - pathology; Biological and medical sciences; Cell Cycle - drug effects; Cell Division - drug effects; Cells, Cultured; Diseases of the osteoarticular system; Humans; Inflammatory joint diseases; Interleukin-1 - antagonists & inhibitors; Interleukin-4 - pharmacology; Medical sciences; Platelet-Derived Growth Factor - antagonists & inhibitors; Receptors, Interleukin-4; Receptors, Mitogen - physiology; Synovial Membrane - drug effects; Synovial Membrane - pathology; Human; Immunopathology; Synovitis; Secretion; Acute; Cytokine; Diseases of the osteoarticular system; Autoimmune disease; Inflammatory joint disease; Immune regulation; Interleukin 4; Rheumatoid arthritis; Cell cycle; Models; Growth factor
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.151.9.4908

A major feature of rheumatoid arthritis is an uncontrolled proliferation of synoviocytes. This is consistent with the active production of factors such as platelet-derived growth factor (PDGF) and IL-1 by the synovitis, which act in vivo as well as in vitro as potent synoviocyte growth factors. We have previously shown that IL-4 is able to inhibit growth factor production in an ex vivo model of synovitis. Herein, we show that IL-4 strongly inhibited PDGF and IL-1 beta stimulated rheumatoid arthritis synoviocyte proliferation in a dose-dependent manner and through its 130 kDa receptor. This antiproliferative effect of IL-4 directly correlated with a blockade of the synoviocyte cell cycle at the G0 + G1 phases. We also observed that IL-4 induced striking morphologic changes in IL-1 beta or PDGF-stimulated synoviocytes, including increased volume and granulosity. These changes led to major perturbations of the cell monolayer, associated with a marked decrease of synoviocyte viability. Taken together, these data indicate that IL-4 inhibits growth factor-induced proliferation of synoviocytes by interfering with the cell cycle, and by decreasing cell survival.