Role of IL-2 and IL-4 in exacerbations of murine antigen-induced arthritis

Immunology. 1994 Nov;83(3):390-6.


In this study the roles of different T-cell subsets, and produced cytokines, were investigated in an animal model for acute exacerbations. Flare-up reactions are inducible in the chronic phase of a smouldering antigen-induced inflammation by injection of a small amount of an antigen into a hyper-reactive knee joint. In vivo treatment with anti-CD4 monoclonal antibodies (mAb) almost totally blocked the flare reaction, whereas anti-CD8 treatment did not exert any effect. The role of T-helper 1 (Th1) cells in delayed-type hypersensitivity-resembling diseases is generally entitled proinflammatory, whereas Th2 cells act in an anti-inflammatory manner. To investigate the role of these T-cell subsets in flare-up reactions, anti-interleukin-2 (IL-2) and anti-IL-4 mAb treatments were performed. Anti-IL-2 treatment partly blocked the flare reaction, and anti-IL-4 treatment, although the result was unexpected, blocked the flare more efficiently. Furthermore, when human recombinant IL-2 (hrIL-2) and murine recombinant IL-4 (mrIL-4) were co-injected with the antigen to test their ability respectively to potentiate or down-regulate the flare reaction, both cytokines demonstrated additional pro-inflammatory effects, although hrIL-2 was more potent than mrIL-4. The mere effect of hrIL-2 and mrIL-4 was studied by direct injection into a hyperreactive joint. No flare-up reaction or cell-influx could be induced, suggesting that other mediators are needed to exert pro-inflammatory effects of IL-2 or IL-4. We conclude that not only Th1 cells, but also Th2 lymphocytes (at least regarding IL-4 production) may play a pro-inflammatory role in flare-up reactions of chronic arthritis. Considering therapeutic application of Th2 cell-derived cytokines, one should be aware of the possible pro-inflammatory potential of IL-4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Arthritis / immunology*
  • Female
  • Immunization
  • Interleukin-2 / physiology
  • Interleukin-4 / physiology
  • Interleukins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antibodies, Monoclonal
  • Interleukin-2
  • Interleukins
  • Interleukin-4