title: Interleukin-1 receptor antagonist modulates inflammation and scarring after ligament injury.
abstract: Ligaments have limited regenerative potential and as a consequence, repair is protracted and results in a mechanically inferior tissue more scar-like than native ligament. We previously reported that a single injection of interleukin-1 receptor antagonist (IL-1Ra) delivered at the time of injury, decreased the number of M2 macrophage-associated inflammatory cytokines. Based on these results, we hypothesized that IL-1Ra administered after injury and closer to peak inflammation (as would occur clinically), would more effectively decrease inflammation and thereby improve healing. Since IL-1Ra has a short half-life, we also investigated the effect of multiple injections. The objective of this study was to elucidate healing of a medial collateral ligament (MCL) with either a single IL-1Ra injection delivered one day after injury or with multiple injections of IL-1Ra on days 1, 2, 3, and 4. One day after MCL injury, rats received either single or multiple injections of IL-1Ra or PBS. Tissue was then collected at days 5 and 11. Both single and multiple IL-1Ra injections reduced inflammatory cytokines, but did not change mechanical behavior. A single injection of IL-1Ra also reduced the number of myofibroblasts and increased type I procollagen. Multiple IL-1Ra doses provided no additive response and, in fact, reduced the M2 macrophages. Based on these results, a single dose of IL-1Ra was better at reducing the MCL-derived inflammatory cytokines compared to multiple injections. The changes in type I procollagen and myofibroblasts further suggest a single injection of IL-1Ra enhanced repair of the ligament but not sufficiently to improve functional behavior.
authors.affiliation: Department of Orthopedics and Rehabilitation and.
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: Sarah E
authors.initials: SE
authors.lastname: Duenwald-Kuehl
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Brickson
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Baer
authors.forename: Ray
authors.initials: R
authors.lastname: Vanderby
mesh_terms: D000818:Animals; D007249:Inflammation / Q000188:drug therapy; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D008022:Ligaments / Q000293:injuries*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1