SELECTIVE CYTOPHERESIS DEVICES AND RELATED METHODS THEREOF
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 system for treating leukocytes, the system comprising:
a device defining a passageway for flowing a biological sample, the passageway comprising a region configured to sequester a leukocyte originating from the sample; and
an agent capable of inhibiting release of a pro-inflammatory substance from the leukocyte or deactivating the leukocyte.
2 . The system of claim 1 , further comprising a second device in series with the device defining the passageway.
3 . The system of claim 1 , wherein the agent is associated with a surface of the passageway.
4 . The system of claim 1 , wherein the agent is infused into the passageway.
5 . The system of claim 1 , wherein the agent comprises a calcium chelating agent.
6 . The system of claim 5 , wherein the calcium chelating agent comprises citrate.
7 . The system of claim 1 , wherein the agent comprises an immunosuppressant agent, a serine leukocyte inhibitor, nitric oxide, a polymorphonuclear leukocyte inhibitor factor, a secretory leukocyte inhibitor, and a calcium chelating agent, wherein the calcium chelating agent is one or more of group consisting of citrate, sodium hexametaphosphate, ethylene diamine tetra-acetic acid (EDTA), triethylene tetramine, diethylene triamine, o-phenanthroline, and oxalic acid.
8 . The system of claim 1 , wherein the region configured to sequester the leukocyte comprises a membrane.
9 . The system of claim 8 , wherein the membrane is porous.
10 . The system of claim 8 , wherein the membrane has a surface area greater than about 0.2 m 2 .
11 . The system of claim 1 , wherein the region configured to sequester the leukocyte is configured such that shear force within the region is less than about 1000 dynes/cm 2 .
12 . The system of claim 1 , wherein the region configured to sequester the leukocyte comprises a cell-adhesion molecule.
13 . A method for processing a leukocyte contained within a body fluid, the method comprising:
(a) sequestering extracorporeally a primed or activated leukocyte; and
(b) treating the leukocyte to inhibit release of a pro-inflammatory substance or to deactivate the leukocyte.
14 . The method of claim 13 , wherein the leukocyte is sequestered for a time sufficient to inhibit the release of the pro-inflammatory substance or to deactivate the leukocyte.
15 . The method of claim 13 , wherein the leukocyte is sequestered for a prolonged period of time.
16 . The method of claim 15 , wherein the leukocyte is sequestered for at least one hour.
17 . The method of claim 13 , further comprising the step of returning the leukocyte produced in step (b) back to a subject.
18 . The method of claim 13 , wherein in step (b), a calcium chelator inhibits the release of the pro-inflammatory substance or deactivates the leukocyte.
19 . A method for treating a subject at risk of developing or having an inflammatory condition, the method comprising:
(a) sequestering extracorporeally a primed or activated leukocyte from the subject; and
(b) treating the leukocyte to reduce the risk of developing inflammation associated with the inflammatory condition or to alleviate inflammation associated with the inflammatory condition.
20 . The method of claim 19 , wherein the inflammatory condition is selected from the group consisting of systemic inflammatory response syndrome (SIRS), cardiopulmonary bypass syndrome, acute respiratory distress syndrome (ARDS), sepsis, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, psoriasis, allograft rejection, asthma, chronic renal failure, cardiorenal syndrome, hepatorenal syndrome, and acute organ failure from ischemic reperfusion injury to myocardium, central nervous system, liver, kidney, or pancreas.
21 - 42 . (canceled)