Methods of using interleukin-1 receptor antagonist as a myeloprotective agent
The present invention relates to uses of interleukin-1 receptor antagonist (IL-1Ra) in promoting bone marrow regeneration, increasing peripheral white blood cells, and increasing platelet levels in subjects if administered prior to treatment with chemotherapeutic agents. Thus, particular embodiments of the invention are directed to uses of IL-1Ra as an adjuvant or ancillary therapy to alleviate the hematopoietic toxicities associated with chemotherapy.
1. A method for providing myeloprotection to a subject in need of chemotherapy, the method comprising:
(a) administering an effective amount of interleukin-1 receptor antagonist to a subject; and
(b) following step (a), administering a chemotherapeutic agent to the subject; wherein following the administering of the chemotherapeutic agent, the subject has increased bone marrow cell density, increased platelet level, or increased peripheral white blood cell level compared to a subject not administered the interleukin-1 receptor antagonist.
2. The method of claim 1 , wherein the interleukin-1 receptor antagonist is administered subcutaneously.
3. The method of claim 1 , wherein the administering of the interleukin-1 receptor antagonist occurs once a day for one to five days prior to the subject receiving the chemotherapeutic agent.
4. The method of claim 1 , wherein the administering of the interleukin-1 receptor antagonist occurs once a day for two to five days prior to the subject receiving the chemotherapeutic agent.
5. The method of claim 1 , wherein the effective amount is from 0.1 to 10 mg of interleukin-1 receptor antagonist per kg body weight of the subject.
6. The method of claim 1 , wherein the effective amount is from 0.5 to 1.5 mg of interleukin-1 receptor antagonist per kg body weight of the subject.
7. The method of claim 1 , wherein the interleukin-1 receptor antagonist is human interleukin-1 receptor antagonist.
8. The method of claim 7 , wherein the interleukin-1 receptor antagonist is human interleukin-1 receptor antagonist according to SEQ ID NO: 1 or SEQ ID NO: 7.
9. The method of claim 1 , wherein the interleukin-1 receptor antagonist is a biologically active variant having at least 95% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 2.
10. The method of claim 1 , wherein the chemotherapeutic agent is cell cycle specific.
11. The method of claim 10 , wherein the chemotherapeutic agent is selected from the group consisting of 5-fluorouracil, arabinofuranosyl cytidine (Ara-C), vinblastine, and methotrexate.
12. The method of claim 1 , wherein the chemotherapeutic agent is cell cycle non-specific.
13. The method of claim 12 , wherein the chemotherapeutic agent is selected from the group consisting of: cyclophosphamide, doxorubicin, cisplatin, and busulfan.
14. The method of claim 1 , wherein the subject is a human.
15. The method of claim 1 , further comprising administering a hematopoietic growth factor to the subject following the chemotherapeutic agent.
16. The method of claim 15 , wherein the growth factor is granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF).