title: Interleukin-6 as an inflammatory mediator and target of therapy in chronic periaortitis.
abstract: OBJECTIVE
  Chronic periaortitis (CP) usually responds to glucocorticoids, but some patients have glucocorticoid-refractory disease or contraindications to glucocorticoid therapy. This study was undertaken to evaluate treatment with the anti-interleukin-6 receptor (anti-IL-6R) antibody tocilizumab in 2 patients with CP, one with refractory disease and the other with contraindications to glucocorticoids, and to assess IL-6 levels in an additional cohort of patients with CP.
  
  
  METHODS
  Both patients were given intravenous tocilizumab (8 mg/kg) once every 4 weeks for 6 months. Serum IL-6 was measured in 22 patients with active CP and 16 healthy controls. Tissue IL-6 expression was assessed by confocal microscopy in biopsy specimens obtained from 6 patients with CP.
  
  
  RESULTS
  In the first patient, whose disease was refractory to various immunosuppressive treatments, tocilizumab added to ongoing therapy with prednisone and methotrexate allowed prednisone withdrawal and induced resolution of symptoms, acute-phase reactant normalization, and reduction in (18) F-fluorodeoxyglucose ((18) F-FDG) uptake on positron emission tomography. The patient experienced a relapse 7 months later and was successfully retreated with tocilizumab. In the second patient, who was unable to tolerate glucocorticoids because of psychiatric side effects, tocilizumab monotherapy induced sustained clinical and laboratory remission, (18) F-FDG uptake disappearance, and CP shrinkage. Serum IL-6 levels were significantly higher in patients with active CP than in controls (P < 0.0001), and IL-6 was abundantly expressed in biopsy specimens from CP patients, particularly by T cells, B cells, histiocytes, fibroblasts, and vascular smooth muscle cells.
  
  
  CONCLUSIONS
  Tocilizumab may be a therapeutic option for CP. The systemic and tissue up-regulation of IL-6 in CP, together with the clinical benefit of IL-6R blockade observed in our 2 patients, suggest that IL-6 may contribute to CP pathogenesis.
authors.affiliation: University Hospital of Parma, Parma, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.forename: Maria G
authors.initials: MG
authors.lastname: Catanoso
authors.forename: Lucia
authors.initials: L
authors.lastname: Spaggiari
authors.forename: Luca
authors.initials: L
authors.lastname: Magnani
authors.forename: Nicolò
authors.initials: N
authors.lastname: Pipitone
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Macchioni
authors.forename: Lia
authors.initials: L
authors.lastname: Pulsatelli
authors.forename: Maria
authors.initials: M
authors.lastname: Nicastro
authors.forename: Gabriella
authors.initials: G
authors.lastname: Becchi
authors.forename: Domenico
authors.initials: D
authors.lastname: Corradi
authors.forename: Annibale
authors.initials: A
authors.lastname: Versari
authors.forename: Luigi
authors.initials: L
authors.lastname: Boiardi
authors.forename: Carlo
authors.initials: C
authors.lastname: Salvarani
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D012185:Retroperitoneal Fibrosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab