Selective cytopheresis devices and related methods thereof
View Patent ↗The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.
1. A method for processing a leukocyte contained within a body fluid from a subject with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), the method comprising:
(a) sequestering extracorporeally a primed or activated leukocyte; and
(b) treating the leukocyte sequestered during step (a) with a calcium chelating agent to inhibit release of a pro-inflammatory substance from the leukocyte or to deactivate the leukocyte.
2. The method of claim 1 , wherein the leukocyte is sequestered for a time sufficient to inhibit the release of the pro-inflammatory substance from the leukocyte or to deactivate the leukocyte.
3. The method of claim 1 , wherein the leukocyte is sequestered for at least one hour.
4. The method of claim 1 , further comprising the step of permitting the leukocyte produced in step (b) to return back to the subject.
5. The method of claim 1 , wherein the calcium chelating agent comprises citrate.
6. The method of claim 1 , wherein the calcium chelating agent ameliorates inflammation associated with the primed or activated leukocyte.
7. The method of claim 1 , wherein step (a) is performed using a device defining a passageway comprising a region configured to sequester the leukocyte.
8. The method of claim 7 , wherein the calcium chelating agent is infused in the passageway.
9. The method of claim 8 , wherein the calcium chelating agent comprises citrate.
10. The method of claim 7 , wherein the region configured to sequester the leukocyte comprises a membrane.
11. The method of claim 10 , wherein the leukocyte binds to a surface of the membrane.
12. The method of claim 10 , wherein the membrane is porous.
13. The method of claim 10 , where the membrane has a surface area greater than about 0.2 m 2 .
14. The method of claim 7 , wherein the region configured to sequester the leukocyte is configured so that shear force within the region is less than about 1000 dynes/cm 2 when fluid passes through the passageway at a rate of from about 100 mL/minute to about 500 mL/minute.
15. The method of claim 14 , wherein the region configured to sequester the leukocyte is configured so that shear force within the region is less than about 100 dynes/cm 2 when fluid passes through the passageway at a rate of from about 100 mL/minute to about 500 mL/minute.
16. The method of claim 14 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent for less than an hour.
17. The method of claim 14 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent from 1 to 24 hours.
18. The method of claim 7 , wherein the leukocyte binds to a surface of the region.
19. The method of claim 1 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent for less than an hour.
20. The method of claim 1 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent from 1 to 24 hours.
21. A method for treating inflammation in a subject with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), the method comprising:
(a) sequestering extracorporeally a primed or activated leukocyte in a body fluid from the subject; and
(b) treating the leukocyte sequestered during step (a) with a calcium chelating agent to inhibit release of a pro-inflammatory substance from the leukocyte or to deactivate the leukocyte, thereby to treat inflammation in the subject.
22. The method of claim 21 , wherein step (a) is performed using a device defining a passageway comprising a region configured to sequester the leukocyte.
23. The method of claim 22 , wherein the calcium chelator is infused into the passageway.
24. The method of claim 23 , wherein the calcium chelating agent comprises citrate.
25. The method of claim 22 , wherein the region configured to sequester the leukocyte comprises a membrane.
26. The method of claim 25 , wherein the membrane is porous.
27. The method of claim 25 , wherein the membrane has a surface area greater than about 0.2 m 2 .
28. The method of claim 25 , wherein the leukocyte binds to a surface of the membrane.
29. The method of claim 22 , wherein the region configured to sequester the leukocyte is configured so that shear force within the region is less than about 100 dynes/cm 2 when fluid passes through the passageway at a rate of from about 100 mL/ minute to about 500 mL/minute.
30. The method of claim 29 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent for less than an hour.
31. The method of claim 22 , wherein the leukocyte binds to a surface of the region.
32. The method of claim 21 , further comprising the step of permitting the leukocyte produced in step (b) to return back to the subject.
33. The method of claim 21 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent for less than an hour.
34. The method of claim 21 , wherein step (b) comprises exposing the leukocyte to the calcium chelating agent from 1 to 24 hours.
35. The method of claim 21 , wherein the calcium chelating agent ameliorates an inflammatory response associated with the primed or activated leukocyte.
36. The method of claim 35 , wherein the calcium chelating agent is citrate.
37. The method of claim 36 , wherein the leukocyte is sequestered for a time sufficient to inhibit the release of the pro-inflammatory substance from the leukocyte or to deactivate the leukocyte.
38. The method of claim 37 , wherein the leukocyte is sequestered for at least one hour.