IL-1 beta, IL-6, KC and MCP-1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis.
The hallmark of haemophilia is the joint morbidity resulting from haemarthrosis that accounts for the majority of the bleeds. The exact mechanisms underlying changes are not fully elucidated. Cytokines are speculated to be involved in the progression and in vitro studies have confirmed the presence of elevated levels of cytokines in synovial tissue and cartilage from patients with haemophilic synovitis. In this study, the presence of selected cytokines in synovial fluid from haemophilia A mice with experimentally induced haemarthroses treated with rFVIII, rFVIIa and an rFVIIa analogue were investigated. Ten cytokines previously shown to be involved in arthritic syndromes were evaluated. Interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, IL-17, Tumor Necrosis Factor-alpha (TNF- alpha), keratinocyte-derived chemokine (KC), Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) were included. In this article, we demonstrate, for the first time, that bleeding in knee joints of haemophilia A mice resulted in correlated increased levels of the pro-inflammatory cytokines: IL-1 beta, IL-6, KC and the MCP-1 in synovial fluid. These results suggest an important role of MCP-1 in the recruitment of monocytes and furthermore that the inflamed synovium releases IL-1 beta, IL-6 and KC, which in turn might contribute to further progression of the inflammatory process.
Øvlisen
K
K
Haemostasis Pharmacology, Novo Nordisk A/S, Novo Nordisk Park, Dk-2760 Måløv, Denmark. saq@novonordisk.com
Kristensen
A T
AT
Jensen
A L
AL
Tranholm
M
M
D000818:Animals; D018932:Chemokine CCL2; D005169:Factor VIII / Q000008:administration & dosage; D015942:Factor VIIa / Q000008:administration & dosage; D006395:Hemarthrosis / Q000188:drug therapy / Q000276:immunology*; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D053583:Interleukin-1beta / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007596:Joints / Q000187:drug effects*; D051379:Mice; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*
D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D010446:Peptide Fragments; D011994:Recombinant Proteins; C508645:monocyte chemoattractant protein 1 (66-77); C052994:interleukin-1beta (163-171); C078147:F8 protein, human; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa