Device, system, and method for controllably reducing inflammatory mediators in a subject

1. An extracorporeal device comprising:

a treatment chamber including at least one flow route configured to receive and return peripheral blood of a subject;

at least one sensor configured to detect one or more inflammatory mediators in the peripheral blood of the subject;

at least one reservoir containing one or more reactive biological or chemical compounds that alter a functional structure of the one or more inflammatory mediators; and

a controller in communication with the at least one sensor and the at least one reservoir and configured to modulate release of the one or more reactive biological or chemical compounds from the at least one reservoir and into the peripheral blood to substantially attain a target value of the detected one or more inflammatory mediators in the peripheral blood of the subject.

2. The device of claim 1 , wherein the one or more reactive biological or chemical compounds includes a denaturing agent, a degradative agent or a binding agent.

3. The device of claim 2 , wherein the one or more reactive biological or chemical compounds decreases an activity of one or more of anaphylatoxins, cytokines, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

4. The device of claim 2 , wherein the denaturing agent includes an acid, base, solvent, cross-linking agent, chaotropic agent, disulfide bond reducer, enzyme, drug, cell, or radical ion.

5. The device of claim 2 , wherein the degradative agent includes at least one of an enzyme, coenzyme, enzyme complex, catalytic antibody, proteasome, strong acid, strong base, radical, photoactivatable agent, drug, cell, or radical ion.

6. The device of claim 5 , wherein the catalytic antibody generates the radical ion.

7. The device of claim 2 , wherein the one or more binding agents on a matrix adapted to the treatment chamber are configured to sequester at least one of the one or more inflammatory mediators from the blood.

8. The device of claim 2 , wherein the one or more binding agents include one or more of antibodies, receptors, or cognates and binds to at least one of the one or more inflammatory mediators.

9. The device of claim 2 , wherein the one or more binding agents include one or more of lectin, binding protein, catalytic antibody, catalytic aptamer, protease conjugate, or photoactivatable agent conjugate.

10. The device of claim 1 , wherein the one or more reactive biological or chemical compounds decreases an activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

11. The device of claim 1 , wherein the one or more reactive biological or chemical compounds modulates an activity of an intermediate that modulates an activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

12. The device of claim 11 , wherein the one or more reactive biological or chemical compounds increases an activity of an intermediate that decreases an activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

13. The device of claim 11 , wherein the one or more reactive biological or chemical compounds decreases an activity of an intermediate that decreases the activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

14. The device of claim 1 , wherein the target value includes a desired concentration of the one or more inflammatory mediators in the peripheral blood.

15. The device of claim 1 , wherein the target value includes a desired range of concentrations of the one or more inflammatory mediators in the peripheral blood.

16. The device of claim 1 , wherein the target value includes a desired ratio of concentrations of two or more inflammatory mediators in the peripheral blood.

17. The device of claim 1 , wherein the target value includes a desired ratio of levels of two or more inflammatory mediators in the peripheral blood.

18. The device of claim 1 , wherein the at least one sensor and the controller are configured to control levels of the one or more inflammatory mediators to achieve the target value.

19. The device of claim 1 , wherein the controller is configured to control interaction between the one or more reactive components and the one or more inflammatory mediators in the treatment chamber.

20. The device of claim 1 , wherein the controller is configured to control access to the treatment chamber by the peripheral blood.

21. The device of claim 1 , wherein the at least one sensor includes a biosensor, chemical sensor, physical sensor, or optical sensor.

22. The device of claim 21 , wherein the at least one sensor includes one or more of an aptamer, antibody, or receptor.

23. The device of claim 21 , wherein the at least one sensor includes one or more of a recognition-based substrate, an aptamer-based substrate, an antibody-based substrate, surface plasmon resonance, genetically-modified cells, or genetically-modified cells with receptor-linked signaling.

24. The device of claim 23 , wherein the genetically-modified cells include receptor-linked signaling by fluorogen-activating proteins.

25. The device of claim 1 , wherein the at least one sensor is configured to detect cytokines, T-lymphocytes, B-lymphocytes, or antibodies.

26. The device of claim 1 , wherein the at least one sensor is configured to detect body temperature, vital signs, edema, oxygen level, or pathogen/toxin level of the subject.

27. The device of claim 1 , wherein the at least one sensor is configured to detect anaphylatoxins, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

28. The device of claim 27 , wherein the at least one sensor is configured to detect TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxins or endotoxins.

29. The device of claim 1 , wherein the device includes a dialysis device, hemoperfusion device, apheresis device, intravenous device, or patch device.

30. The device of claim 1 , wherein the at least one sensor includes at least one physical sensor.

31. The device of claim 30 , wherein the at least one physical sensor includes at least one of a recognition-based substrate, an aptamer-based substrate, an antibody-based substrate, or surface plasmon resonance.

32. A system comprising:

an extracorporeal device including a treatment chamber configured to receive peripheral blood of a subject through a flow route, the treatment chamber including one or more reactive biological or chemical compounds that alter a functional structure of one or more inflammatory mediators in the peripheral blood of the subject; and

at least one sensor configured to detect the one or more inflammatory mediators in the peripheral blood and configured to provide an output related thereto; and

a controller configured to receive the output of the at least one sensor and configured to control interaction between the one or more biological or chemical compounds and the one or more inflammatory mediators in the treatment chamber by modulating release of the one or more reactive biological or chemical compounds into the treatment chamber;

wherein the at least one sensor and the controller function relative to a target value of at least one of the one or more inflammatory mediators in the peripheral blood.

33. The system of claim 32 , wherein the one or more reactive biological or chemical compounds includes a denaturing agent, a degradative agent or a binding agent.

34. The system of claim 32 , wherein the one or more reactive biological or chemical compounds decreases an activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

35. The system of claim 32 , wherein the one or more reactive biological or chemical compounds increases an activity of an intermediate that decreases the activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

36. The system of claim 32 , wherein the one or more reactive biological or chemical compounds decreases an activity of an intermediate that decreases the activity of one or more of TNF-α, IL-1, IL-1β, IL-6, IL-8, IL-10, IL-12, LPB, IFN-γ, LIF, MIF, MIP-1, MCP-1, C3-a, C5-a, exotoxin, or endotoxin.

37. The system of claim 33 , wherein the one or more reactive biological or chemical compounds decreases an activity of one or more of anaphylatoxins, cytokines, chemokines, leukotrienes, prostaglandins, complement, coagulation factors, or proinflammatory cytokines.

38. An extracorporeal device comprising:

a treatment chamber configured to receive peripheral blood of a subject through a flow route;

at least one sensor configured to detect one or more inflammatory mediators in the peripheral blood of the subject;

at least one reservoir containing one or more modulators that alter a functional structure of the one or more inflammatory mediators; and

a controller in communication with the at least one sensor and the at least one reservoir and configured to adjust release of the one or more modulators from the at least one reservoir and into the peripheral blood to substantially attain a target value of the detected one or more inflammatory mediators in the peripheral blood of the subject.