title: The influence of interleukin-4 on ligament healing.
abstract: 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.
authors.affiliation: Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin 53705, USA.
authors.forename: Connie S
authors.initials: CS
authors.lastname: Chamberlain
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Leiferman
authors.forename: Kayt E
authors.initials: KE
authors.lastname: Frisch
authors.forename: Sijian
authors.initials: S
authors.lastname: Wang
authors.forename: Xipei
authors.initials: X
authors.lastname: Yang
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Brickson
authors.forename: Ray
authors.initials: R
authors.lastname: Vanderby
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D003094:Collagen; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D042783:Endothelial Cells; D006097:Granulation Tissue / Q000502:physiology; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000494:pharmacology* / Q000502:physiology; D008022:Ligaments / Q000187:drug effects / Q000293:injuries* / Q000502:physiology*; D018655:Lymphocyte Count; D008297:Male; D017888:Medial Collateral Ligament, Knee / Q000187:drug effects / Q000293:injuries / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D024042:Collagen Type I; D024061:Collagen Type III; D015847:Interleukin-4; D003094:Collagen