WO1996036350B1

WO1996036350B1 - Use of il-13 to induce 15-lipoxygenase

Info

Publication number: WO1996036350B1
Application number: PCT/US1996/006779
Authority: WO
Filing date: 1996-05-13
Publication date: 1997-01-03
Anticipated expiration: 1997-11-19

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

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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.

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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.