Methods and compositions for the treatment of sterile inflammation
Described are methods and compositions that inhibit IL-1 signalling for the treatment of acute inflammatory response to cell necrosis, and the attendant collateral tissue damage.
1. A method of treating or delaying development or progression of sterile inflammation caused by necrosis in a subject, the method comprising administering to the subject a therapeutically effective amount of an antisense oligonucleotide or a small interfering RNA (siRNA) that specifically inhibits expression of Myeloid Differentiation Primary Response Gene 88 (MyD88).
2. The method of claim 1 , further comprising:
detecting the presence of necrotic cells or tissues in a subject who has, or is at risk of having sterile inflammation; and
selecting the subject if necrotic cells are present.
3. The method of claim 1 , wherein the sterile inflammation caused by necrosis is sterile inflammation associated with pancreatitis.
4. The method of claim 1 , wherein the sterile inflammation caused by necrosis is sterile inflammation associated with ischemic injury.
5. The method of claim 4 , wherein the ischemic injury is an injury to cardiac tissue, uterine tissue, renal tissue, hepatic tissue, neural tissue, muscle tissue, dermal tissue, or other organ.
6. The method of claim 4 , wherein the ischemic injury is caused by a surgical intervention.
7. The method of claim 1 , wherein the sterile inflammation caused by necrosis is caused by organ transplantation procedure.
8. The method of claim 7 , wherein the necrosis is in the transplanted organ.
9. The method of claim 1 , wherein the administration is local administration to the necrotic cells or a tissue or organ comprising the necrotic cells.
10. The method of claim 1 , wherein the administration is local.