Intradiscal production of autologous interleukin antagonist
Administering a buffy coat and immunoglobulin into a disc to induce the production of interleukin receptor antagonist protein IRAP within the disc is disclosed.
1 . A method of administering IRAP to a patient, comprising:
a) obtaining from the patient a physiologic fluid comprising viable cells,
b) mixing an IRAP-inducing composition comprising an immunoglobulin with at least a portion of the physiologic fluid thereby producing an Ig-rich fluid, and
c) administering an effective amount of the Ig-rich fluid to a location in the patient to induce the viable cells therein to in vivo produce IRAP at the location.
2 . The method of claim 1 wherein the portion of the physiologic fluid is a blood fraction.
3 . The method of claim 1 wherein the portion of the blood fraction is a buffy coat.
4 . The method of claim 1 wherein the portion of the physiologic fluid is platelet-rich plasma.
5 . The method of claim 1 wherein the portion of the physiologic fluid comprises a buffy coat and platelet-poor plasma.
6 . The method of claim 1 wherein the physiologic fluid is whole blood.
7 . The method of claim 1 wherein the portion of the physiologic fluid comprises fibrinogen.
8 . The method of claim 1 wherein the viable cells are monocytes.
9 . The method of claim 1 wherein the viable cells are taken from the patient's blood.
10 . The method of claim 1 wherein the viable cells are chondrocytes.
11 . The method of claim 1 wherein the viable cells are neutrophils.
12 . The method of claim 1 wherein the viable cells are disc cells.
13 . The method of claim 1 wherein the viable cells are nucleus pulposus cells.
14 . The method of claim 1 wherein the viable cells are annulus fibrosus cells.
15 . The method of claim 1 wherein the viable cells are present in a concentrated form.
16 . The method of claim 1 wherein the viable cells are autologous.
17 . The method of claim 1 wherein the immunoglobulin is selected from the group consisting of IgA, IgG, and mixtures thereof.
18 . The method of claim 1 wherein the immunoglobulin is IgA.
19 . The method of claim 1 wherein the immunoglobulin is IgG.
20 . The method of claim 1 wherein the IRAP-inducing composition comprises IgA and IgG.
21 . The method of claim 1 wherein the IRAP-inducing composition comprises at least 50% IgA, as measured against a sum of immunoglobulin in the composition.
22 . The method of claim 1 wherein the IRAP-inducing composition comprises at least 70% IgA, as measured against a sum of immunoglobulin in the composition.
23 . The method of claim 1 wherein the physiologic fluid is housed within a mixing container during step b).
24 . The method of claim 23 wherein the IRAP-inducing composition is a solubilizable coating upon a wall of the mixing container.
25 . The method of claim 23 wherein the IRAP-inducing composition is a solubilizable powder located within the container.
26 . The method of claim 23 wherein the mixing container is a syringe.
27 . The method of claim 1 wherein the mixing step is carried out in less than 10 hours.
28 . The method of claim 1 wherein the mixing step is carried out in less than 1 hour.
29 . The method of claim 1 wherein the induction produces an in vivo IRAP concentration of at least 10 ng/ml IRAP.
30 . The method of claim 1 wherein the induction produces an in vivo IRAP concentration of at least 25 ng/ml IRAP.
31 . The method of claim 1 wherein the induction produces an in vivo IRAP concentration of at least 50 ng/ml IRAP.
32 . The method of claim 1 wherein the location further comprises IL- 10 , and the induction produces an in vivo IRAP: IL-1β ratio of at least 1000:1.
33 . The method of claim 1 wherein the location further comprises IL-1β, and the induction produces an in vivo IRAP: IL-1β ratio of at least 10,000:1.
34 . The method of claim 1 wherein the Ig-rich fluid is injected into a joint.
35 . The method of claim 1 wherein the Ig-rich fluid is injected into an intervertebral disc.
36 . The method of claim 1 wherein the Ig-rich fluid is injected into a nucleus pulposus of the intervertebral disc.
37 . The method of claim 1 wherein the Ig-rich fluid further comprises platelet releasate.
38 . The method of claim 1 wherein the Ig-rich fluid further comprises stem cells.
39 . The method of claim 1 wherein the Ig-rich fluid further comprises fibrinogen.
40 . The method of claim 1 wherein the Ig-rich fluid further comprises thrombin.
41 . The method of claim 1 wherein the Ig-rich fluid is substantially free of cells.
42 . A method of treating degenerative disc disease in an intervertebral disc having a nucleus pulposus and an annulus fibrosus, comprising the steps of:
a) intradiscally administering an effective amount of a formulation comprising an IRAP-inducing composition comprising an immunoglobulin into the intervertebral disc.
43 . A method of treating sciatica, comprising the steps of:
a) epidurally administering an effective amount of a formulation comprising an IRAP-inducing composition comprising an immunoglobulin in the vicinity of a nerve root.
44 . A centrifugation container adapted for centrifuging blood comprising a side wall having at least one side port disposed therein.
45 . The centrifugation container of claim 42 wherein the side port comprises a puncturable gasket adapted for receiving a needle.
46 . The centrifugation container of claim 42 wherein the side wall has a plurality of side ports, each port comprising a puncturable gasket adapted for receiving a needle.
47 . The centrifugation container of claim 42 wherein the plurality of side ports are vertically aligned.
48 . A method of producing IRAP, comprising:
a) obtaining from the patient a physiologic fluid comprising viable cells,
b) mixing an IRAP-inducing composition comprising IgA with at least a portion of the physiologic fluid thereby producing an Ig-rich fluid.
49 . The method of claim 48 further comprising the step of:
c) allowing the Ig-rich fluid to produce IRAP ex vivo, and
d) administering an effective amount of the IRAP to a location in the patient.
50 . The method of claim 48 further comprising the step of:
c) administering an effective amount of the Ig-rich fluid to a location in the patient to induce the viable cells therein to in vivo produce IRAP at the location.