The Role of Interleukin-4 and Interleukin-10 in Osteoarthritic Joint Disease: A Systematic Narrative Review

E M van Helvoort, E van der Heijden, J A G van Roon, N Eijkelkamp, S C Mastbergen

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)
7 Downloads (Pure)


OBJECTIVE: A fusion protein of interleukin-4 and interleukin-10 (IL4-10 FP) was developed as a disease-modifying osteoarthritis drug (DMOAD), and chondroprotection, anti-inflammation, and analgesia have been suggested. To better understand the mechanisms behind its potential as DMOAD, this systematic narrative review aims to assess the potential of IL-4, IL-10 and the combination of IL-4 and IL-10 for the treatment of osteoarthritis. It describes the chondroprotective, anti-inflammatory, and analgesic effects of IL-4, IL-10, and IL4-10 FP.

DESIGN: PubMed and Embase were searched for publications that were published from 1990 until May 21, 2021 (moment of search). Key search terms were: Osteoarthritis, Interleukin-4, and Interleukin-10. This yielded 2,479 hits, of which 43 were included in this review.

RESULTS: IL-4 and IL-10 showed mainly protective effects on osteoarthritic cartilage in vitro and in vivo, as did IL4-10 FP. Both cytokines showed anti-inflammatory effects, but also proinflammatory effects. Only in vitro IL4-10 FP showed purely anti-inflammatory effects, indicating that proinflammatory effects of one cytokine can be counteracted by the other when given as a combination. Only a few studies investigated the analgesic effects of IL-4, IL-10 or IL4-10 FP. In vitro, IL-4 and IL4-10 FP were able to decrease pain mediators. In vivo, IL-4, IL-10, and IL4-10 FP were able to reduce pain.

CONCLUSIONS: In conclusion, this review describes overlapping, but also different modes of action for the DMOAD effects of IL-4 and IL-10, giving an explanation for the synergistic effects found when applied as combination, as is the case for IL4-10 FP.

Original languageEnglish
Article number19476035221098167
Pages (from-to)1-14
Issue number2
Publication statusPublished - 1 Apr 2022


  • Analgesics/therapeutic use
  • Animals
  • Anti-Inflammatory Agents/pharmacology
  • Cytokines/metabolism
  • Disease Models, Animal
  • Interleukin-10/pharmacology
  • Interleukin-4/pharmacology
  • Osteoarthritis/drug therapy
  • Pain/drug therapy
  • interleukins
  • osteoarthritis
  • osteoarthritis disease modification


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