title: Cytokine-induced tendinitis: a preliminary study in rabbits.
abstract: This study was designed to determine the effects of a single injection of a species-specific preparation of cytokines into rabbit patellar tendons and to compare the results with a known model of tendinitis, the collagenase-injection model. New Zealand White rabbits were divided into two groups and two time periods (4 and 16 weeks) and injected in the midsubstance of the right patellar tendon with either cytokines or collagenase under ultrasound guidance to confirm intratendinous needle placement. The left patellar tendon was injected with 0.025 ml of saline solution and served as a control. The rabbits were returned to cage activity after injection. At death, two rabbits in each group underwent histological analysis; the remaining eight animals in each time frame were evaluated biomechanically and then biochemically with use of the patella/whole patellar tendon/tibia complex. Histologic results at 4 weeks in the tendons injected with cytokines demonstrated increased cellularity, which was resolving by 16 weeks. The matrix appeared unchanged. The tendons injected with collagenase demonstrated increased angiogenesis of the matrix, hypercellularity, and fibrosis around the tendon at 4 weeks. At 16 weeks, myxoid changes, focal fibrosis, and collagen-bundle disarray with persistent increase in cellularity were noted. Biomechanically, a significant decrease in ultimate load at 16 weeks was seen in the tendons injected with cytokines but no change was seen in cross-sectional area. The tendons injected with collagenase demonstrated a significant increase in cross-sectional area at 4 and 16 weeks compared with those injected with cytokines. Biochemically, there was no significant difference in collagen content between the two groups at 4 or 16 weeks but the tendons injected with collagenase demonstrated a significant increase in crosslinking at 16 weeks. Our conclusion is that the tendons injected with the cytokine preparation represent a model of mild, seemingly reversible tendon injury. The cytokine preparation produces no matrix damage or evidence of collagen degradation and is species specific.
authors.affiliation: Musculoskeletal Research Center, University of Pittsburgh Medical Center, Pennsylvania 15213, USA. dstone@uoi.upmc.edu
authors.forename: D
authors.initials: D
authors.lastname: Stone
authors.forename: C
authors.initials: C
authors.lastname: Green
authors.forename: U
authors.initials: U
authors.lastname: Rao
authors.forename: H
authors.initials: H
authors.lastname: Aizawa
authors.forename: T
authors.initials: T
authors.lastname: Yamaji
authors.forename: C
authors.initials: C
authors.lastname: Niyibizi
authors.forename: G
authors.initials: G
authors.lastname: Carlin
authors.forename: S L
authors.initials: SL
authors.lastname: Woo
mesh_terms: D000818:Animals; D003094:Collagen / Q000032:analysis; D017364:Collagenases / Q000008:administration & dosage / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000032:analysis; D016207:Cytokines / Q000009:adverse effects*; D004195:Disease Models, Animal; D006614:Hindlimb; D007267:Injections; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000187:drug effects; D010329:Patella / Q000000981:diagnostic imaging; D011725:Pyridines / Q000032:analysis; D011817:Rabbits; D013045:Species Specificity; D052256:Tendinopathy / Q000139:chemically induced* / Q000473:pathology; D013708:Tendon Injuries / Q000139:chemically induced / Q000473:pathology; D013710:Tendons / Q000737:chemistry / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D014463:Ultrasonography
chemical_list: D003432:Cross-Linking Reagents; D016207:Cytokines; D011725:Pyridines; C023500:3-hydroxypyridine; D003094:Collagen; D017364:Collagenases