Cytokine Targeting/Immunomodulation Program

Leo A.B. Joosten

Program Leader

Email: [email protected]

Research Program

The Program’s Goals are to investigate:

The role of interleukin (IL)-1 and tumor necrosis factor (TNF) in chronic arthritis and concomitant cartilage destruction. This is investigated by targeting IL-1 and TNF or the use of IL-1/TNF deficient mice. In collaboration with G. Kollias the role of membrane bound TNF and TNF receptor deficiency is examined.

The role of IL-4 in cartilage and bone destruction. Overexpression of IL-4 in arthritic joints revealed to protect against cartilage and bone destruction. The mechanism of this protection is one of the goals in this project. The role of IL-17 and osteoprotegerin ligand (OPGL) in this pathway is under investigation.

The relation between gut flora and arthritis expression. There is ample evidence that bacterial infections can lead to arthritis expression. In this program the role of different gut flora is examined on arthritis expression and severity. The immune stimulatory effects of different bacteria will be analyzed.

Modulation of arthritis by induction of bystander suppression with cartilage derived autoantigens. Nasal tolerance induction with either collagen type II, HC gp-39 or COMP will be studied. The possible role of cytokines during tolerance induction is investigated.

Participating researchers and their projects

Erik Lubberts, PhD

Exploration of the protective effect of interleukin-4 on cartilage and bone destruction.

Marleen Heuvelmans-Jacobs, PhD Student

The role of gut flora on arthritis expression.

Marije Koenders, PhD Student

The role of interleukin-17 in arthritis.



  1. Lubberts E, Joosten LAB, Chabaud M, van den Bersselaar L, Coenen-de Roo CJJ, Richards CD, Miossec P, van den Berg WB. Prevention of bone erosion in murine collagen arthritis by local IL-4 gene therapy. Implications in human rheumatoid arthritis. J Clin Invest 2000, in press.
  2. Joosten LAB, Helsen MMA, Saxne T, van de Loo FAJ, Heinegard D, van den Berg WB. IL-1I,b blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNFI blockade only ameliorates joint inflammation. J Immunol 1999;163:5049-55.
  3. Lubberts E, Joosten LAB, van den Bersselaar L, Helsen MMA, Bakker AC, van Meurs JBJ, Graham FL, Richards CD, van den Berg WB. Adenoviral vector-mediated overexpression of IL-4 in the knee joint of mice with collagen-induced arthritis prevents cartilage destruction. J Immunol 1999;163:4546-56.
  4. Joosten LAB, Lubberts E, Helsen MMA, Saxne T, Coenen-de Roo CJJ, Heinegard D, van den Berg WB. Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis [peer-reviewed primary research]. 26oct99/ar0101p03.
  5. Joosten LAB, Coenen-de Roo CJJ, Lubberts E, Helsen MMA, Boots AMH, van den Berg WB, Miltenburg AMM. Intranasal tolerance induction with human cartilage gp-39 ameliorates clinical, histological and radiological signs of collagen type II induced arthritis in DBA-1 mice. Arthritis Rheum 2000, in press.

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