Compositions and methods for treatment of intracellular damage and bacterial infection
Pre-implantation factor (PIF) may be used to treat intracellular damage. Aspects of the invention are directed to a method of treating intracellular damage comprising administering PIF to a subject in need thereof. Some aspects may be directed to methods of increasing cytokine secretion in response to intracellular damage comprising administering PIF to a subject in need thereof. The intracellular damage may be a result of a disease such as Listeria monocytogenes infection, malaria, Lyme disease, cardiovascular disease, duodenal peptic ulcer, atherosclerosis, peritonitis or tuberculosis. In some aspects, a method of treating tuberculosis is disclosed, comprising administering PIF to a subject in need thereof. In some aspects, a method of treating atherosclerosis is disclosed, comprising administering PIF to a subject in need thereof. In some aspects, a method of treating peritonitis is disclosed, comprising administering PIF to a subject in need thereof.
1. A method of treating atherosclerosis comprising administering to a subject in need thereof a therapeutically effective amount of a pre-implantation factor (PIF) peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3.
2. The method of claim 1 further comprising administering a potassium channel inhibitor.
3. The method of claim 2 , wherein the potassium channel inhibitor is a Kv1.3 inhibitor.
4. The method of claim 2 , wherein the potassium channel inhibitor is IFNγ.
5. The method of claim 1 , wherein atherosclerotic plaque is reduced.
6. The method of claim 5 , wherein atherosclerotic plaque is reduced in an aortic arch, an aortic root, or combinations thereof.
7. The method of claim 1 , wherein monocyte proteins are reduced in an aortic arch, an aortic root, or combinations thereof.
8. The method of claim 7 , wherein the monocyte proteins are selected from one or more of vascular cell adhesion molecules, monocyte chemotactic proteins, and clusters of differentiation.
9. The method of claim 8 , wherein the monocyte proteins are selected from one or more of VCAM-1, MCP-1, and CD68.
10. The method of claim 1 , wherein levels of lipids are reduced in an aortic arch, an aortic root, or combinations thereof.
11. The method of claim 10 , wherein levels of circulating lipids is not substantially affected.
12. The method of claim 1 , wherein cytokines are reduced in THP-1 cells, an aortic arch, an aortic root, or combinations thereof.
13. The method of claim 12 , wherein the cytokines are selected from one or more of interleukin 12, subunit beta (IL-12b) and interferon gamma (IFNγ).
14. The method of claim 1 , wherein the therapeutically effective amount is from about 0.1 mg/kg to about 5.0 mg/kg of the subject.
15. The method of claim 1 , wherein the number of foam cells are reduced in an aortic arch, an aortic root, or combinations thereof.
16. A method of reducing atherosclerotic plague and/or inhibiting atherosclerotic lesion development in a subject, comprising administering to the subject a therapeutically effective amount of a PIF peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3.
17. The method of claim 16 , wherein the PIF peptide is SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof.
18. A method of decreasing recruitment to and/or retention of monocytes within an atherosclerotic lesion in a subject, comprising administering to the subject a therapeutically effective amount of a PIF peptide selected from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3.
19. The method of claim 18 , wherein the PIF peptide is SEQ ID NO: 3 or a pharmaceutically acceptable salt thereof.
20. The method of claim 18 , wherein the atherosclerotic lesion is located in an aortic arch, an aortic root, or combinations thereof.