Publication: IL-6 receptor antagonist as adjunctive therapy with clotting factor replacement to protect against bleeding-induced arthropathy in hemophilia
Issued Date
2013-05-01
Resource Type
ISSN
15387836
15387933
15387933
Other identifier(s)
2-s2.0-84877918087
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Thrombosis and Haemostasis. Vol.11, No.5 (2013), 881-893
Suggested Citation
N. Narkbunnam, J. Sun, G. Hu, F. C. Lin, T. A. Bateman, M. Mihara, P. E. Monahan IL-6 receptor antagonist as adjunctive therapy with clotting factor replacement to protect against bleeding-induced arthropathy in hemophilia. Journal of Thrombosis and Haemostasis. Vol.11, No.5 (2013), 881-893. doi:10.1111/jth.12176 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32366
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
IL-6 receptor antagonist as adjunctive therapy with clotting factor replacement to protect against bleeding-induced arthropathy in hemophilia
Abstract
Background: The most common morbidity that results from hemophilia is bleeding-induced hemophilic arthropathy (HA), which once established may not be interrupted completely even by prophylactic clotting factor replacement. Specific therapies to oppose inflammatory cytokines, including Interleukin 6 (IL-6) receptor antagonists, have become important in the management of inflammatory arthritides. Objectives: We investigated combining therapy using MR16-1, a rat IgG antibody directed against mouse IL-6 receptor (anti-IL-6R), with factor VIII (FVIII) replacement to protect against bleeding-induced arthropathy in hemophilia A mice. Methods: Three recurrent hemarthroses were induced in the knee joint capsule of FVIII knockout mice. Treatment at the time of each hemorrhage included either: no treatment; FVIII replacement given at the time of hemorrhage; FVIII replacement at hemorrhage plus anti-IL-6R as 4-weekly injections; FVIII replacement with non-specific control antibody (rat IgG); and anti-IL-6R alone without FVIII replacement. Six weeks following the first hemarthosis, joints were harvested and histopathology was scored for synovitis, for cartilage integrity and for macrophage infiltration. Results: Animals that received anti-IL-6R as an adjunct to FVIII replacement demonstrated the best survival and the least acute joint swelling and pathology on histologic examination of the synovium and cartilage (P < 0.05 for each parameter). All histopathologic parameters in the mice receiving FVIII+anti-IL-6R were limited and were comparable to findings in injured hemostatically normal mice. The major benefits of adjunctive anti-IL-6R were decreasing synovial hyperplasia, hemosiderin deposition and macrophage infiltration. Conclusions: Short-course specific inhibition of inflammatory cytokines as an adjunct to replacement hemostasis may be an approach to minimize hemophilic joint degeneration. © 2013 International Society on Thrombosis and Haemostasis.