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THU0029 Effect of il-4 on il-1 induced intracellular ca2+ changs and inhibition of pg synthesis in articular chondrocytes
  1. F Nishisaka1,
  2. K Fukuda2,
  3. S Soenn3,
  4. M Saito1,
  5. M Oh1,
  6. T Matsushita1,
  7. H Kikuchi1
  1. 1Orthopaedic Surgery, Sakai Hospital, Kinki University, School of Medicine, Sakai
  2. 2Orthopaedic Surgery, Kinki University, School of Medicine, Osakasayama
  3. 3Orthopaedic Surgery, Nara Hospital, Kinki University, School of Medicine, Ikoma, Japan


Background Studies suggest that interleukin-1 (IL-1) is the key mediator of arthritis and we have investigated the effect of IL-1 on cartilage degradation. We demonstrated that IL-1 inhibited proteoglycan (PG) synthesis via enhanced nitric oxide (NO) synthesis by chondrocytes. We also demonstrated that IL-1 increased intracellular Ca2+ ion concentration ([Ca2+]i) of chondrocytes. On the other hand, interleukin-4 (IL-4) is a T-cell derived 20 kDa glycoprotein and antagonise the cytokine mediated cartilage degradation.

Objectives We examined the effect of IL-4 on IL-1-enhanced NO synthesis in parallel with intracellular Ca levels and PG synthesis.

Methods Bovine articular chondrocytes were obtained. PG synthesis was measured with [35S] sulfate incorporation. NO levels were measured by use of an NO chemiluminescence analyzer. Ca2+ imaging was carried out with Fura2-AM loaded chondrocyte using the digital fluorescence-imaging system.

Results In the presence of IL-4, IL-1-enhanced NO release was completely abolished. IL-4 functions mainly as anti-inflammatory, as well as IL-10 and IL-13. To our knowledge, this is the first report demonstrating an inhibitory effect of IL-4 in NO release stimulated by IL-1. Alterations in [Ca2+]i provide a ubiquitous cell signalling system that mediates a variety of cellular process. IL-1 evoked an increase in the levels of [Ca2+]i, a response characterised by a steep onset and followed by a slower decline to preexisting values. IL-4 also abolished the IL-1-induced [Ca2+]i increase in the chondrocytes. We examined the effect of IL-4 on PG synthesis. Although IL-4 did not affect PG synthesis, IL-1-inhibited PG synthesis was reversed with the addition of IL-4. It is possible that IL-4 reversed the IL-1-inhibited PG synthesis through the inhibition of NO synthesis and [Ca2+]i increase.

Conclusion IL-4 plays a chondroprotecting effect antagonising with IL-1-inhibited PG synthesis.


  1. Yeh LA, Augustine AJ, Lee P, Riviere LR, Sheldon A. Interleukin-4, an inhibitor of cartilage breakdown in bovine articular cartilage explants. J Rheumatol. 1995;22(9):1740–6

  2. Fukuda K, Kumano F, Takayama M, Saito M, Otani K, Tanaka S. Zonal differences in nitric oxide synthesis by bovine chondrocytes exposed to interleukin-1. Inflamm Res. 1995;44(10):434–7

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