title: Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects.
abstract: BACKGROUND
  Temporomandibular joint (TMJ) arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA) corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits. Blockage of TNF-alpha has already proven its efficacy in children with juvenile idiopathic arthritis not responding to standard therapy. In this paper we evaluate the effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in rabbits on histological changes using histomorphometry and stereology. This article presents the data and discussion on the anti-inflammatory effects of systemic and IA etanercept. In Part II the data on the effects of systemic and IA etanercept on facial growth are presented.
  
  
  METHODS
  Forty-two rabbits (10 weeks old) pre-sensitized with ovalbumin and locally induced inflammation in the temporomandibular joints were divided into three groups: a placebo group receiving IA saline injections in both joints one week after arthritis induction (n = 14), an IA etanercept group receiving 0.1 mg/kg etanercept per joint one week after arthritis induction (n = 14) and a systemic etanercept group receiving 0.8 mg/kg etanercept weekly throughout the 12-week study (n = 14). Arthritis was maintained by giving four inductions three weeks apart. Additional IA saline or etanercept injections were also given one week after the re-inductions. Histomorphometric and unbiased stereological methods (optical fractionator) were used to assess and estimate the inflammation in the joints.
  
  
  RESULTS
  The histomorphometry showed synovial proliferation in all groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating with systemic etanercept but not with IA etanercept. Semi-quantitative assessments of synovial proliferation and subsynovial inflammation also showed reduced inflammation in the systemic etanercept group. However, the thickness of the synovial lining and volume of the subsynovial connective tissue showed no differences between the groups.
  
  
  CONCLUSIONS
  An anti-inflammatory effect of systemic etanercept on the synovial tissues in the temporomandibular joint was shown. However, IA etanercept at the given dose had no significant effect on the severity of chronic inflammation on the parameters here tested in ovalbumin antigen-induced arthritis.
authors.affiliation: Department of Orthodontics, Faculty of Health Sciences, University of Aarhus, Vennelyst Boulevard 9, 8000 Aarhus C, Denmark. kdahl@odont.au.dk.
authors.forename: Kasper D
authors.initials: KD
authors.lastname: Kristensen
authors.forename: Peter
authors.initials: P
authors.lastname: Stoustrup
authors.forename: Annelise
authors.initials: A
authors.lastname: Küseler
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Pedersen
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
authors.forename: Ellen
authors.initials: E
authors.lastname: Hauge
authors.forename: Troels
authors.initials: T
authors.lastname: Herlin