Patent
Use of PPAR.gamma. agonists for inhibition of inflammatory cytokine production
| العنوان: | Use of PPAR.gamma. agonists for inhibition of inflammatory cytokine production |
|---|---|
| Patent Number: | 5,925,657 |
| تاريخ النشر: | July 20, 1999 |
| Appl. No: | 08/878,406 |
| Application Filed: | June 18, 1997 |
| مستخلص: | Disclosed herein are methods for reducing or preventing cytokine production associated with an inflammatory response, involving administering to a mammal a therapeutically-effective amount of a thiazolidinedione PPAR.gamma. agonist. |
| Inventors: | Seed, Brian (Boston, MA); Jiang, Chengyu (Boston, MA) |
| Assignees: | The General Hospital Corporation (Boston, MA) |
| Claim: | What is claimed is |
| Claim: | 1. A method for reducing or preventing inflammatory cytokine production associated with rheumatoid arthritis in a mammal, said method comprising administering to said mammal a thiazolidinedione PPAR.gamma. agonist in an amount which is sufficient to produce a 50% inhibition of cytokine production in a mammalian monocyte culture. |
| Claim: | 2. A method for reducing or preventing inflammatory cytokine production associated with inflammatory bowel disease in a mammal, said method comprising administering to said mammal a therapeutically-effective amount of a thiazolidinedione PPAR.gamma. agonist. |
| Claim: | 3. A method for reducing or preventing inflammatory cytokine production associated with an immunodeficiency syndrome in a mammal, said method comprising administering to said mammal a therapeutically-effective amount of a thiazolidinedione PPAR.gamma. agonist. |
| Claim: | 4. A method for reducing or preventing inflammatory cytokine production associated with multiple sclerosis in a mammal, said method comprising administering to said mammal a therapeutically-effective amount of a thiazolidinedione PPAR.gamma. agonist. |
| Claim: | 5. A method for reducing or preventing inflammatory cytokine production associated with cachexia in a mammal, said method comprising administering to said mammal a therapeutically-effective amount of a thiazolidinedione PPAR.gamma. agonist. |
| Claim: | 6. The method of claim 5, wherein said cachexia results from a neoplasia. |
| Claim: | 7. The method of claim 5, wherein said cachexia results from a chronic infectious disease. |
| Claim: | 8. The method of claim 1, 2, 3, 4, or 5, wherein said thiazolidinedione is troglitazone. |
| Claim: | 9. The method of claim 1, 2, 3, 4, or 5, wherein said cytokine is TNF.alpha., IL-1.beta., or IL-6. |
| Claim: | 10. The method of claim 1, 2, 3, 4, or 5, wherein said cytokine is produced by a monocyte. |
| Claim: | 11. The method of claim 1, 2, 3, 4, or 5, wherein said thiazolidinedione PPAR.gamma. agonist is administered orally. |
| Claim: | 12. The method of claim 2, 3, 4, or 5, wherein said thiazolidinedione PPAR.gamma. agonist is administered in an amount which is sufficient to produce a 50% inhibition of cytokine production in a mammalian monocyte culture. |
| Current U.S. Class: | 514/369; 514/370; 514/340; 514/366; 514/365 |
| Current International Class: | A01N 4378; A61K 31425 |
| Patent References Cited: | 5594015 January 1997 Kurtz et al. |
| Other References: | Chemical Abstracts AN 1997:653205, Peraldi et al. Oct. 1997. Chemical Abstracts AN 1994:692489, Ohsumi et al., Jan. 1994. Chawla et al., "Peroxisome proliferator-activated receptor (PPAR) .gamma.:adipose-predominant expression and induction early in adipocyte differentiation," Endocrinol. 135:798-800, 1994. Forman et al., "15-deoxy-.DELTA..sup.12, 14 -prostaglandin J.sub.2 is a ligand for the adipocyte determination factor PPAR.gamma.," Cell 83:803-812, 1995. Hu et al., "Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR.gamma. and C/EBP.alpha.," Proc. Natl. Acad. Sci. USA 92:9856-9860, 1995. Kliewer et al., "A rostaglandin J.sub.2 metabolite binds peroxisome proliferator-activated receptor .gamma. and promotes adipocyte differentiation," Cell 83:813-819, 1995. Lehmann et al., "An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor .gamma. (PPAR.gamma.)," J. Biol Chem. 270:12953-12956, 1995. Lehmann et al., "Peroxisome proliferator-activated receptors .alpha. and .gamma. are activated by indomethacin and other non-steroidal andti-inflammatory drugs," J. Biol. Chem. 272:3406-3410, 1997. Tontonoz et al., "mPPAR.gamma.2: tissue-specific regulator of an adipocyte enhancer," Genes Dev. 8:1224-1234, 1994. Tontonoz et al., "Stimulation of adipogenesis in fibroblasts by PPAR.gamma.2, a lipid-avtivated transcription factor," Cell 79:1147-1156, 1994. Peraldi et al., "Thiazolidinediones block tumor necrosis factor-.alpha.-induced inhibition of insulin signaling," J. Clin invest, 100:1863-1869, 1997. Ohsumi et al., "Troglitazone prevents the inhibitory effects of inflammatory cytokines in insulin-induced adipocyte differentiation in 3T3-L1 cells," Endocrinology, 135:2279-2282, 1994. |
| Primary Examiner: | MacMillan, Keith D. |
| Attorney, Agent or Firm: | Clark & Elbing LLP |
| رقم الانضمام: | edspgr.05925657 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |