Abstract
In this study, we sought to improve ligament healing by modulating the inflammatory response after acute injury through the neutralization of Interleukin-17 (IL-17), which we hypothesized would decrease inflammatory cell infiltration and cytokine production. Administration of an Interleukin-17 neutralizing antibody (IL-17 NA) immediately following a rat medial collateral ligament (MCL) transection resulted in alterations in inflammatory cell populations and cytokine expression within the healing ligament, but did not reduce inflammation. Specifically, treatment resulted in a decrease in M2 (anti-inflammatory) macrophages, an increase in T cells, and an increase in the levels of IL-2, IL-6, and IL-12 in the MCL 7 days post injury. IL-17NA treatment, and subsequent immunomodulation, did not result in improved ligament healing, as measured by collagen composition and wound size.
Highlights
After injury, ligaments never regain their original mechanical or structural properties [1,2]
We hypothesized that blocking IL-17 activity with a neutralizing antibody would impact the inflammatory response and reduce inflammatory cell populations and cytokine production within the healing ligament
NA at the time of ligament injury significantly decreased the number of M2 macrophages in the granulation tissue, significantly increased the number of T cells in the ligament, and significantly increased the levels of IL-2, IL-6, and IL-12 in the medial collateral ligament (MCL) 7 days post injury
Summary
Ligaments never regain their original mechanical or structural properties [1,2]. The repair process results in the formation of a neo-ligament, which is more scar-like in character than the native tissue. Ligament healing is characterized by an infiltration of inflammatory cells including neutrophils and macrophages, followed by fibroblasts, myofibroblasts, and endothelial cells which together form granulation tissue and repair the wound through extracellular matrix (ECM) production via synthesis of type I and type III collagen, resulting in scar formation [3]. Macrophages infiltrate the injured ligament and produce matrix metalloproteinases (MMPs) as well as reactive oxygen and nitrogen species, which degrade collagen as part of the remodeling process and correlate to an increase in the size of the granulation tissue [3,4]. The degradation of healthy ligament and growth of the granulation tissue during remodeling corresponds to the localization of pro-inflammatory M1 macrophages [3]. In order to maintain the beneficial properties of the immune response while limiting the damaging effects of inflammation, we seek to modulate the immune response during ligament healing in order to improve ligament regeneration and reduce scar formation
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