title: Immunomodulatory properties of rumalon, a glycosaminoglycan peptide complex, in patients with osteoarthritis: activation of T helper cell type 2 cytokines and antigen-specific IgG4 antigen-specific igG4 antibodies.
abstract: OBJECTIVE
  To assess the immunogenic properties of the glycosaminoglycan peptide complex Rumalon, an aqueous extract of bovine cartilage and bone marrow frequently used in patients with osteoarthritis (OA).
  
  
  METHODS
  Sera from 31 patients with OA who had received several series of Rumalon injections (Group 1, n = 17: before therapy and after one injection series; Group 2, n = 6: after 2-3 injection series; Group 3, n = 4: after 4-8 injection series; Group 4, n = 4: after 9-18 injection series) were tested by ELISA for antibodies against Rumalon and its components as well as by a double sandwich ELISA for type 1 [interferon-gamma, interleukin 2 (IL-2)] and type 2 cytokines (IL-4, IL-5, IL-10, IL-13).
  
  
  RESULTS
  After the first injection series antibodies to Rumalon were induced in 7 of the 17 patients that were all negative before therapy. The antibodies were preferentially of the IgG4 type. IgG4 levels were increased during therapy (ELISA optical density x 1000 in Group 1: 73.9 +/- 209.5; Group 4: 1354.5 +/- 307.6), and in Group 4 all patients had developed these antibodies. Upon analysis of cytokine levels, there was a significant increase in IL-5 (Group 1 before therapy 407.4 +/- 257.1 pg/ml, Groups 3 and 4: 1409.4 +/- 963.1 pg/ml; p < 0.001) and to a lesser extent of IL-10 during therapy (Group 1 before therapy 950.2 +/- 867.8 pg/ml, Groups 3 and 4: 2817.8 +/- 3127.3 pg/ml; p < 0.05), while type 1 cytokines were not affected.
  
  
  CONCLUSIONS
  Rumalon appears to have immunomodulatory properties and preferentially stimulates IgG4 antibodies via the activation of type 2 cytokines in vivo. Whether these phenomena can be correlated with the postulated therapeutic effect of Rumalon in patients with OA remains to be seen, but pain relief via release of endorphins by Th2 cells could be one explanation.
authors.affiliation: Department of Internal Medicine II, University of Tübingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Klein
authors.forename: E W
authors.initials: EW
authors.lastname: Becker
authors.forename: P A
authors.initials: PA
authors.lastname: Berg
authors.forename: A
authors.initials: A
authors.lastname: Bernau
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002417:Cattle; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014020:Tissue Extracts / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D007074:Immunoglobulin G; D010455:Peptides; D014020:Tissue Extracts; C000562:Rumalon