Article ; Online: Mortality, cardiac and cerebral damages reduction by IL-1 inhibition in a murine model of TTP.
2024
Abstract: Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in Von Willebrand factor cleavage resulting in capillary microthrombi formation and ischemic organ damage. Interleukin-1 (IL-1), has been shown to ... ...
| Abstract | Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in Von Willebrand factor cleavage resulting in capillary microthrombi formation and ischemic organ damage. Interleukin-1 (IL-1), has been shown to drive sterile inflammation following ischemia and could play an essential contribution to post-ischemic organ damage in TTP. Our objectives were to evaluate IL-1 involvement during TTP and to test the efficacy of the recombinant IL-1 receptor antagonist, anakinra, in a murine TTP model. We retrospectively measured plasmatic IL-1 concentrations in TTP patients and controls. TTP patients exhibited elevated plasma IL-1α and β concentrations, which correlated with disease course and survival. In a TTP mouse model, we administered anakinra (IL-1 inhibitor) or placebo for 5 days and evaluated the efficacy of this treatment. Anakinra significantly reduced mortality of mice (P<0.001). Anakinra significantly decreased TTP-induced cardiac damages as assessed by blood troponin concentrations, evaluation of left ventricular function by echocardiography, [18F]FDG PET of myocardial glucose metabolism, and cardiac histology. Anakinra also significantly reduced brain TTP-induced damages, evaluated through blood PS100b concentrations, nuclear imaging and histology. We finally showed that IL-1α and β trigger endothelial degranulation in vitro, leading to the release of Von Willebrand factor. In conclusion, Anakinra significantly reduced TTP mortality in a pre-clinical model of the disease by inhibiting both endothelial degranulation and post-ischemic inflammation, supporting further evaluations in humans. |
|---|---|
| Language | English |
| Publishing date | 2024-04-05 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 80069-7 |
| ISSN | 1528-0020 ; 0006-4971 |
| ISSN (online) | 1528-0020 |
| ISSN | 0006-4971 |
| DOI | 10.1182/blood.2023021974 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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