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|Title:||Cytokine related treatments of disease|
|Abstract:||Nucleosides and other compounds to selectively modulate Th1 and Th2 responses relative to each other in the treatment of disease. In one aspect of the invention, administration of a nucleoside or other compound reduces the dosage at which a primary drug is administered. In another aspect of the invention, an abnormality reflected in increased response in one group of cytokines is treated by administering a nucleoside or other compound that increases response in another group of cytokines. In yet another aspect of the invention, a patient is prophylactically treated by administering a nucleoside or other compound that selectively reduces Th1 activity without significantly reducing Th2 activity. In yet another aspect of the invention, a nucleoside or other compound is administered to a patient at a dose that reduces the patient's GTP pool to a degree that selectively reduces one of the Th1 or Th2 responses without significantly reducing the other response. Controlled release dosage forms are particularly contemplated to achieve that result.|
|Inventor(s):||Tam; Robert (Irvine, CA), Wang; Guangyi (Irvine, CA), Averett; Devron (Irvine, CA), Ramasamy; Kandasamy (Laguna Hills, CA)|
|Assignee:||Ribapharm, Inc. (Costa Mesa, CA)|
|Filing Date:||Dec 20, 1999|
|Claims:||1. A method of selectively modulating Th1 and Th2 responses in a peripheral blood mononuclear cell of a patient infected with a virus comprising: identifying a patient in need of treatment for a viral infection; administering a compound according to formula 1 to the patient ##STR2## |
wherein R.sub.2, R.sub.3, R.sub.7 and R.sub.8 are independently selected from H, OH, CN, N.sub.3, halogens, CH.sub.2 OH, NH.sub.2, OCH.sub.3, NHCH.sub.3, ONHCH.sub.3, SCH.sub.3, SPh, alkenyl, lower alkyl, lower alkyl amines or substituted heterocycles; and administering the compound to the peripheral blood mononuclear cell at a concentration effective to selectively modulate the Th1 and Th2 responses relative to each other.
2. The method of claim 1 wherein the viral infection is selected from the group consisting of an HIV infection, an HCV infection, and a HBV infection.
3. The method of claim 1 wherein the step of administering increases a Th1 response relative to a Th2 response in the peripheral blood mononuclear cell.
4. The method of claim 3 wherein the Th1 response increases.
5. The method of claim 4 wherein the increase in the Th1 response comprises a mean peak increase over an activated control level in IL-2 of at least 20%(by weight).
6. The method of claim 4 wherein the increase in the Th1 response comprises a mean peak increase over an activated control level in IFN-.gamma. of at least 75%(by weight).
7. The method of claim 4 wherein the increase in the Th1 response comprises a mean peak increase over an activated control level in TNF-.alpha. of at least 50%(by weight).
8. The method of claim 4 wherein the increase in the Th1 response comprises a mean peak increase over an activated control level in IL-2, IFN-.gamma., and TNF-.alpha. of 42%(mole), 125%(mole), and 72%(mole), respectively.
9. The method of claim 1 wherein the step of administering comprises in vivo administration.
10. The method of claim 1 wherein the step of administering comprises oral administration.
11. The method of claim 1 wherein the step of administering comprises injection of the L-ribonucleoside.
12. The method of claim 1 wherein the step of administering comprises administering the compound in a dose between 0.1 mg per kg of body weight of the patient and 1.0 mg per kg of body weight of the patient.
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