Role of interleukin-4 and interleukin-10 in murine collagen-induced arthritis. Protective effect of interleukin-4 and interleukin-10 treatment on cartilage destruction

Arthritis Rheum. 1997 Feb;40(2):249-60. doi: 10.1002/art.1780400209.


Objective: To examine the role of endogenous interleukin-4 (IL-4) and interleukin-10 (IL-10) and the therapeutic effect of the addition of IL-4 and IL-10 in early and established murine collagen-induced arthritis (CIA).

Methods: Murine recombinant IL-4, IL-10, or the combination was given intraperitoneally twice daily from the day of arthritis onset up to 7-10 days of CIA in DBA/1 mice. Anti-IL-4, anti-IL-10, or both antibodies were given intraperitoneally before or after the onset of CIA. The effect of cytokine or anticytokine treatment was monitored visually by macroscopic scoring. Histology and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at the end of the treatment period.

Results: IL-4 alone did not provoke any effect, IL-10 slightly suppressed the arthritis, but a more pronounced amelioration was found with the combination. This cooperative effect was noted after early treatment but also occurred when the start of treatment was delayed until 1 week after onset. Apart from suppression of macroscopic signs of inflammation, combined treatment with IL-4/IL-10 also reduced cellular infiltrates in the synovial tissue and caused pronounced protection against cartilage destruction. Moreover, levels of mRNA for tumor necrosis factor alpha (TNF alpha) and IL-1 were highly suppressed both in the synovial tissue and in the articular cartilage. In contrast, levels of IL-1 receptor antagonist (IL-1Ra) mRNA remained elevated, which suggests that the mechanism of protection may be related to suppressed production of TNF alpha and IL-1, with concomitant up-regulation of the IL-1Ra/IL-1 balance. However, accelerated onset of CIA and increased severity could be achieved with neutralizing anti-IL-10 antibodies. This expression could be further optimized with a combination of anti-IL-4 and anti-IL-10 antibodies, although anti-IL-4 alone was without effect.

Conclusion: Our data are consistent with a dominant role of IL-10 in the natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears of potential therapeutic value, not only at the onset, but also in established arthritis.

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / physiopathology*
  • Cartilage Diseases / prevention & control
  • Cattle
  • Collagen / toxicity*
  • Disease Models, Animal
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-10 / physiology*
  • Interleukin-10 / therapeutic use
  • Interleukin-4 / physiology*
  • Interleukin-4 / therapeutic use
  • Knee Joint / immunology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors


  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Collagen