Premium
The influence of interleukin‐4 on ligament healing
Author(s) -
Chamberlain Connie S.,
Leiferman Ellen M.,
Frisch Kayt E.,
Wang Sijian,
Yang Xipei,
Brickson Stacey L.,
Vanderby Ray
Publication year - 2011
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1524-475x.2011.00682.x
Subject(s) - wound healing , granulation tissue , extracellular matrix , medicine , bone healing , interleukin , ligament , fibroblast , in vivo , periodontal fiber , medial collateral ligament , cytokine , microbiology and biotechnology , surgery , in vitro , chemistry , immunology , biology , dentistry , biochemistry
Despite a complex cascade of cellular events to reconstruct the damaged extracellular matrix, ligament healing results in a mechanically inferior scarred ligament. During normal healing, granulation tissue expands into any residual normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise and an inefficient repair process. To control creeping substitution and possibly enhance the repair process, the antiinflammatory cytokine, interleukin‐4 (IL‐4), was administered to rats before and after rupture of their medial collateral ligaments. In vitro experiments showed a time‐dependent effect on fibroblast proliferation after IL‐4 treatment. In vivo treatments with IL‐4 (100 ng/mL IV) for 5 days resulted in decreased wound size and type III collagen and increased type I procollagen, indicating a more regenerative early healing in response to the IL‐4 treatment. However, continued treatment of IL‐4 to day 11 antagonized this early benefit and slowed healing. Together, these results suggest that IL‐4 not only influences the macrophages and T lymphocytes but also stimulates fibroblasts associated with the proliferative phase of healing in a dose‐, cell‐, and time‐dependent manner. Although treatment significantly influenced healing in the first week after injury, IL‐4 alone was unable to maintain this early regenerative response.