Acute Haemarthrosis in the Haemophilia A Rat Generates a Local and Systemic Proinflammatory Response
| Autor: | Wiktor Majewski, Olga Østrup, Kristine Rothaus Christensen, Bo Wiinberg, K. M. Lövgren, Søren Skov |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Eotaxin Male Chemokine Time Factors Haemophilia A Inflammation 030204 cardiovascular system & hematology Hemophilia A Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Arthropathy Hemarthrosis Synovial Fluid Medicine Synovial fluid Animals Genetic Predisposition to Disease Factor VIII biology business.industry Hematology medicine.disease Disease Models Animal 030104 developmental biology Phenotype Immunology biology.protein Cytokines Tumor necrosis factor alpha Female Joints Lymph Nodes medicine.symptom Inflammation Mediators Rats Transgenic business Transcriptome |
| Zdroj: | Thrombosis and haemostasis. 117(11) |
| ISSN: | 2567-689X |
| Popis: | Background Replacement therapy with coagulation factor VIII (FVIII) concurrent with bleeds (on-demand) in haemophilia A (HA) patients has been hypothesized to increase the risk for antidrug antibodies (inhibitors). A danger signal environment, characterized by tissue damage and inflammation at the site of a bleed, is thought to contribute to the anti-FVIII response. The nature of this inflammatory reaction is, however, not fully known, and new insights will be valuable for both managing inhibitors and understanding arthropathy development. Objective To characterize the inflammatory response, locally and systemically, during the first 24 hours following a joint bleed in the HA rat. Methods HA rats received a needle-induced knee joint bleed (n = 83) or a sham procedure (n = 41). Blood samples were collected at selected time points from 0 to 24 hours post injury/sham. Synovial fluid, intra-articular knee tissue and popliteal lymph nodes were collected at 24 hours. Cytokine/chemokine concentrations and gene expression were measured. Results Gene expression analysis revealed a rapid inflammatory response in the injured knees, accompanied by significantly increased levels of specific gene products in the synovial fluid; IL-1β, TNFα, KC/GRO, IL-6, Eotaxin, MCP-1, MCP-3, MIP-1α, MIP-2, RANTES, A2M and AGP. Plasma analysis demonstrated significantly increased systemic levels of KC/GRO and IL-6 in injured rats already after 5 to 6 hours. Conclusion A rapid proinflammatory response, locally and systemically, characteristic of innate immunity, was demonstrated. Results reveal a more comprehensive inflammatory picture than previously shown, with resemblance to human haemophilic arthropathy, and with unique correlation between gene expression level, synovial concentration and plasma concentration in individual rats. |
| Databáze: | OpenAIRE |
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