Effects of exogenous IL-1 β, TNF α, IL-6, IL-8 and LIF on cytokine production by human articular chondrocytes

• Published in: Osteoarthritis and cartilage Vol. 4; no. 3; pp. 163 - 173
• Main Authors: Henrotin, Yves E., De Groote, Donat D., Labasse, Alain H., Gaspar, Simone E., Zheng, Shao-Xiong, Geenen, Vincent G., Reginster, Jean-Yves L.
• Format: Journal Article Web Resource
• Language: English
• Published: England Elsevier Ltd 01.09.1996; W.B. Saunders
• Subjects: Arthritis; Cartilage, Articular - cytology; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cartilage, Articular/cytology/drug effects/metabolism; Cells, Cultured; Chondrocytes; Cytokines; Cytokines - biosynthesis; Cytokines - drug effects; Cytokines/biosynthesis/drug effects; Growth Inhibitors - pharmacology; Human health sciences; Humans; Immunoenzyme Techniques; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Interleukin-8 - pharmacology; Interleukins - pharmacology; Leukemia Inhibitory Factor; Lymphokines - pharmacology; Recombinant Proteins; Rheumatology; Rhumatologie; Sciences de la santé humaine; Tumor Necrosis Factor-alpha - pharmacology; Arthritis; Cytokines; Leukemia inhibitory factor; Chondrocytes
• ISSN: 1063-4584; 1522-9653; 1522-9653
• DOI: 10.1016/S1063-4584(96)80012-4

Cytokines are potent regulators of the chondrocyte functions. Some of them are produced by chondrocytes and interact to regulate cartilage metabolism. In this study, we investigated the production of interleukin-1 β (IL-1 β), IL-6, IL-8 and leukemia inhibitory factor (LIF) by human chondrocytes and examined the modulation of their secretion by exogenous cytokines. Human articular chondrocytes were isolated from their extracellular matrix by a triple successive enzymatic digestion of the cartilage. Subsequently, chondrocytes were stimulated by increased amounts of human recombinant cytokines [IL-1 β, tumour necrosis factor α (TNF α), IL-8, LIF, IL-6]. IL-1 β, IL-6, IL-8 and LIF were assayed into culture media and inside cell extracts by specific enzyme amplified sensitivity immunoassays (EASIAs). Under these experimental conditions, we have identified various interactions between cytokines. IL- β and TNF α highly stimulated IL-6, LIF and IL-8 productions. IL-6 decreased IL-8 synthesis and increased LIF production. IL-8 slightly enhanced IL-6 production. Finally, LIF stimulated IL-1 β, IL-6 and IL-8 productions. Using neutralizing antibodies against IL-1, we demonstrated that the effects of LIF were secondary to the stimulation by LIF of IL-1 β production by the chondrocytes. In conclusion, chondrocytes secrete a variety of immunocompetent cytokines including IL-1 β, IL-6, IL-8 and LIF that can interact to regulate chondrocytes metabolism. These results also define new biological activities of LIF and IL-6, and raise questions concerning their role in the pathogenesis of joint diseases.