WO1996036350B1 - Use of il-13 to induce 15-lipoxygenase - Google Patents
Use of il-13 to induce 15-lipoxygenaseInfo
- Publication number
- WO1996036350B1 WO1996036350B1 PCT/US1996/006779 US9606779W WO9636350B1 WO 1996036350 B1 WO1996036350 B1 WO 1996036350B1 US 9606779 W US9606779 W US 9606779W WO 9636350 B1 WO9636350 B1 WO 9636350B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- activity
- lta
- human
- hydroxylase
- inflammatory condition
- Prior art date
Links
- 102000009515 Arachidonate 15-Lipoxygenase Human genes 0.000 title 1
- 108010048907 Arachidonate 15-lipoxygenase Proteins 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 14
- 230000000694 effects Effects 0.000 claims abstract 11
- 230000004968 inflammatory condition Effects 0.000 claims abstract 8
- 230000001939 inductive effect Effects 0.000 claims abstract 4
- 230000015572 biosynthetic process Effects 0.000 claims abstract 3
- 230000004054 inflammatory process Effects 0.000 claims abstract 3
- 206010061218 Inflammation Diseases 0.000 claims abstract 2
- 210000001616 monocyte Anatomy 0.000 claims abstract 2
- UFPQIRYSPUYQHK-WAQVJNLQSA-N leukotriene A4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(O)=O UFPQIRYSPUYQHK-WAQVJNLQSA-N 0.000 claims 7
- 241001465754 Metazoa Species 0.000 claims 6
- 102000008109 Mixed Function Oxygenases Human genes 0.000 claims 6
- 108010074633 Mixed Function Oxygenases Proteins 0.000 claims 6
- 102100022364 Polyunsaturated fatty acid 5-lipoxygenase Human genes 0.000 claims 6
- 101710156627 Polyunsaturated fatty acid 5-lipoxygenase Proteins 0.000 claims 6
- 230000037396 body weight Effects 0.000 claims 6
- 210000004027 cell Anatomy 0.000 claims 5
- 230000000754 repressing effect Effects 0.000 claims 5
- 150000001875 compounds Chemical class 0.000 claims 2
- 210000005260 human cell Anatomy 0.000 claims 2
- 238000001727 in vivo Methods 0.000 claims 2
- 229930184725 Lipoxin Natural products 0.000 claims 1
- 210000004102 animal cell Anatomy 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 150000002639 lipoxins Chemical class 0.000 claims 1
- 210000002540 macrophage Anatomy 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 241000894007 species Species 0.000 claims 1
- 108090000978 Interleukin-4 Proteins 0.000 abstract 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 1
- 239000012636 effector Substances 0.000 abstract 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- IXAQOQZEOGMIQS-SSQFXEBMSA-N lipoxin A4 Chemical compound CCCCC[C@H](O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCCC(O)=O IXAQOQZEOGMIQS-SSQFXEBMSA-N 0.000 abstract 1
- 230000001717 pathogenic effect Effects 0.000 abstract 1
- 230000037361 pathway Effects 0.000 abstract 1
- 208000024891 symptom Diseases 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
Abstract
The present invention is based on the discovery that IL-13 induces 15-LO in human monocytes. Surprisingly, it has been found that IL-13 is about ten-fold more active, on a molar basis, than IL-4 in inducing 15-LO. IL-13 is therefore an effective therapeutic for inflammatory conditions responsive to products of 15-LO activity, including 15-S-HETE and LXA4. By enhancing endogenous pathways leading to synthesis of endogenous anti-inflammatory molecules, administration of IL-13 results in inhibition of the end effectors of the inflammatory process itself. The underlying strategy is therefore to direct intervention to specific pathogenic molecules, rather than the current method of treating symptoms of inflammation.
Claims
2 2
AMENDED CLAIMS
[received by the International Bureau on 13 November 1996 (13.11.96); original claims 1-6 cancelled; new claims 17-20 added; remaining claims unchanged (2 pages)]
7. A method of treating an inflammatory condition responsive to compounds whose biosynthesis involves 15-LO activity, comprising administering a 15-LO inducing amount of IL-13 to an animal or human with the inflammatory condition.
8. The method of claim 7 wherein compounds whose biosynthesis involves 15-LO activity are selected from the group consisting of 15-S-HETE or a lipoxin.
9. The method of claim 7 wherein a 15-LO inducing amount of IL-13 is a daily dose in the range 10 ng/kg body weight to 1 mg/kg body weight.
10. A method of treating an animal or human having an inflammatory condition mediated by monocyte/macrophage activity, comprising administering an effective amount of IL-l 3 to said animal or human.
11. The method of claim 10 wherein an effective amount of IL-l 3 is a daily dose in the range 10 ng/kg body weight to 1 mg/kg body weight.
12. A method of repressing 5-LO or LTA4 hydroxylase in animal or human cells comprising the step of administering a repressing amount of IL-l 3 to said cells.
13. The method of claim 12 wherein the IL-13 is of the same species as the cells.
14. The method of claim 12 wherein the IL-l 3 is administered to human cells.
15. The method of claim 12 wherein IL-13 is administered to said cell in vivo.
16. The method of claim 12 wherein IL-13 is administered to said cells ex vivo.
17. The method of claim 15 wherein IL-13 is administered to said cells in vivo at a daily dose range of 10 ng/kg body weight to 1 mg/kg body weight.
18. A method of treating an inflammatory condition increased by 5-LO activity or LTA4 hydroxylase activity comprising administering a 5-LO or LTA4 hydroxylase- repressing amount of IL-13 to an animal or human with the inflammatory condition.
19. A method of using IL-l 3 for the manufacmre of a medicament for repressing 5- LO or LTA4 hydroxylase in a patient with an inflammatory condition enhanced by 5-LO or LTA4 hydroxylase activity.
20. A composition for inducing 15-LO activity and repressing 5-LO and LTA4 hydroxylase activity in a human or animal having an inflammatory condition comprising IL-13 and a pharmaceutically acceptable diluent.
2 4
STATEMENT UNDER ARTICLE 19
Claims 1-6 are withdrawn. No part of the description or the drawings are deemed superfluous, since they provide support for the remaining unchanged claims and newly added claims.
New claims 17-20 have basis in the data of Figs. 5-8 and accompanying description of the figure, especially at page 10. Also disclosed are specific effects of IL-13 on 5-LO and LTA4 hydroxylase expression and their effects on inflammation at page 14 and at page 3 as well as Figure 1. Further support and experimental detail is found in the Examples and elsewhere throughout the description.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU60224/96A AU6022496A (en) | 1995-05-19 | 1996-05-13 | Use of il-13 to induce 15-lipoxygenase |
| JP8534942A JPH11505247A (en) | 1995-05-19 | 1996-05-13 | Use of IL-13 to induce 15-lipoxygenase |
| EP96917810A EP0831889A4 (en) | 1995-05-19 | 1996-05-13 | USE OF IL-13 TO INDUCE 15-LIPOXYGENASE |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/445,311 | 1995-05-19 | ||
| US08/445,311 US5830453A (en) | 1995-05-19 | 1995-05-19 | Use of IL-13 to induce 15-lipoxygenase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996036350A1 WO1996036350A1 (en) | 1996-11-21 |
| WO1996036350B1 true WO1996036350B1 (en) | 1997-01-03 |
Family
ID=23768427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1996/006779 WO1996036350A1 (en) | 1995-05-19 | 1996-05-13 | Use of il-13 to induce 15-lipoxygenase |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US5830453A (en) |
| EP (1) | EP0831889A4 (en) |
| JP (2) | JPH11505247A (en) |
| AU (1) | AU6022496A (en) |
| CA (1) | CA2221449A1 (en) |
| WO (1) | WO1996036350A1 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6509313B1 (en) * | 1996-02-28 | 2003-01-21 | Cornell Research Foundation, Inc. | Stimulation of immune response with low doses of cytokines |
| US6242473B1 (en) * | 1999-01-08 | 2001-06-05 | Maxim Pharmaceuticals, Inc. | Treatment and prevention of reactive oxygen metabolite-mediated cellular damage |
| WO2001077332A2 (en) * | 2000-04-07 | 2001-10-18 | Heska Corporation | Compositions and methods related to canine igg and canine il-13 receptors |
| JP4676054B2 (en) * | 2000-10-16 | 2011-04-27 | 友昭 星野 | Obesity and obesity-related disease therapeutic agent and evaluation method thereof |
| WO2003007685A2 (en) | 2001-07-17 | 2003-01-30 | University Of Florida | Detecting and treating reproductive tract disorders |
| WO2003105824A1 (en) * | 2002-06-14 | 2003-12-24 | Alcon, Inc. | Topical use of hydroxyeicosatetraenoic acid compounds to treat psoriasis |
| US7666411B2 (en) * | 2002-06-14 | 2010-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of treating and preventing colitis involving IL-13 and NK-T cells |
| US8338180B2 (en) | 2003-06-10 | 2012-12-25 | The J. David Gladstone Institutes | Methods for treating lentivirus infections |
| ATE492563T1 (en) * | 2004-11-17 | 2011-01-15 | Amgen Inc | COMPLETE HUMAN MONOCLONAL ANTIBODIES AGAINST IL-13 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5079261A (en) * | 1989-04-28 | 1992-01-07 | Brigham And Women's Hospital | Use of lipoxin a4 and its derivatives as antagonists for slow-reacting substances of anaphylaxis |
| CA2142860A1 (en) * | 1992-08-21 | 1994-03-03 | Gregorio Aversa | Human interleukin-13 |
-
1995
- 1995-05-19 US US08/445,311 patent/US5830453A/en not_active Expired - Fee Related
-
1996
- 1996-05-13 JP JP8534942A patent/JPH11505247A/en not_active Ceased
- 1996-05-13 CA CA002221449A patent/CA2221449A1/en not_active Abandoned
- 1996-05-13 WO PCT/US1996/006779 patent/WO1996036350A1/en not_active Application Discontinuation
- 1996-05-13 EP EP96917810A patent/EP0831889A4/en not_active Withdrawn
- 1996-05-13 AU AU60224/96A patent/AU6022496A/en not_active Abandoned
-
2005
- 2005-02-01 JP JP2005025745A patent/JP2005120111A/en active Pending
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