Method of modulating inflammatory response

• US 20030223969A1
• Filed: 02/25/2003
• Published: 12/04/2003
• Est. Priority Date: 03/15/2002
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: University of Michigan
• Inventors: Humes, H. David
• Granted Patent: US 7,442,546 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3475 with filtrate treatment agent in the same enclosure as the membrane
• CPC Class Codes: A61M 1/3489 by biological cells, e.g. bioreactor
• CPC Class Codes: A61M 1/3623 Means for actively controlling temperature of blood
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 5/00 Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor; plant reproduction by tissue culture techniques A01H4/00

Abstract

A method of immunomodulation by contacting the bodily fluid of a patient with renal tubule cells outside of the kidney.

Claims

1. A method of modulating the levels of at least one inflammatory cytokine in a patient in need thereof, comprising:

contacting, outside of the kidney, at least a portion of the body fluid of the patient with renal tubule cells.

2. The method of claim 1, wherein the patient in need thereof is suffering from one or more disease selected from the group consisting of end-stage renal disease, chronic renal insufficiency, acute renal failure, sepsis, malnutrition, chronic congestive heart failure, inflammatory bowel disease, Crohn'"'"'s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, systemic vasculitis, lupus, Wegener'"'"'s granulomatosis, polyarteritis nodosa, dermatomyositis, diabetes mellitus Type I, thyroiditis, psoriasis, Guillian Barre syndrome, multiple sclerosis, and atherosclerosis, or other autoimmune disorders.

3. The method of claim 2, wherein the patient in need thereof is suffering from one or more disease selected from the group consisting of end-stage renal disease, chronic renal insufficiency, acute renal failure, and sepsis.

4. The method of claim 2, wherein the patient in need thereof is suffering from one or more disease selected from the group consisting malnutrition, chronic congestive heart failure, inflammatory bowel disease, Crohn'"'"'s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, systemic vasculitis, lupus, Wegener'"'"'s granulomatosis, polyarteritis nodosa, dermatomyositis, diabetes mellitus Type I, thyroiditis, psoriasis, Guillian Barre syndrome, multiple sclerosis, and atherosclerosis, or other autoimmune disorders.

5. The method of claim 2, wherein the patient in need thereof is suffering from one or more disease selected from inflammatory bowel disease, Crohn'"'"'s disease, and ulcerative colitis.

6. The method of claim 2, wherein the patient in need thereof is suffering from one or more disease selected from rheumatoid arthritis and ankylosing spondylitis.

7. The method of claim 2, wherein the patient in need thereof is suffering from one or more disease selected from systemic vasculitis, lupus, Wegener'"'"'s granulomatosis, polyarteritis nodosa, and dermatomyositis.

8. The method of claim 2, wherein the patient in need thereof is suffering from one or more disease selected from Guillian Barre syndrome and multiple sclerosis.

9. The method of claim 1, wherein the patient is not afflicted with renal disease.

10. The method of claim 1, wherein the patient is on hemodialysis or peritoneal dialysis.

11. The method of claim 1, wherein the body fluid is blood.

12. The method of claim 1, wherein the body fluid is plasma.

13. The method of claim 1, wherein the body fluid is ultrafiltrate of plasma.

14. The method of claim 1, wherein the body fluid is contacted with the renal tubule cells ex vivo.

15. The method of claim 1, wherein the body fluid is contacted with the renal tubule cells inside the body of the patient.

16. The method of claim 1, wherein the body fluid is contacted with the renal tubule cells in a renal tubule assist device.

17. The method of claim 16, wherein the renal tubule assist device is ex vivo.

18. The method of claim 16, wherein the renal tubule assist device is implanted in the patient.

19. The method of claim 1, wherein the renal tubule cells are in a cell cartridge implanted in a blood vessel of the patient.

20. The method of claim 1, wherein the level of at least one inflammatory cytokine is increased.

21. The method of claim 20, wherein the inflammatory cytokine is a proinflammatory cytokine.

22. The method of claim 21, wherein the proinflammatory cytokine is selected from the group consisting of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, lipopolysaccharide-biding protein, MCP-1, CD-14, GM-CSF, G-CSF and a chemokine.

23. The method of claim 22, wherein the proinflammatory cytokine is TNF-α

.

24. The method of claim 22, wherein the proinflammatory cytokine is IL-1.

25. The method of claim 22, wherein the proinflammatory cytokine is IL-1β

.

26. The method of claim 22, wherein the proinflammatory cytokine is IL-6.

27. The method of claim 22, wherein the proinflammatory cytokine is IL-8.

28. The method of claim 22, wherein the proinflammatory cytokine is lipopolysaccharide-biding protein.

29. The method of claim 22, wherein the proinflammatory cytokine is MCP-1.

30. The method of claim 22, wherein the proinflammatory cytokine is CD-14.

31. The method of claim 22, wherein the proinflammatory cytokine is GM-CSF.

32. The method of claim 22, wherein the proinflammatory cytokine is G-CSF.

33. The method of claim 22, wherein the proinflammatory cytokine is a chemokine.

34. The method of claim 20, wherein the inflammatory cytokine is an anti-inflammatory cytokine.

35. The method of claim 34, wherein the anti-inflammatory cytokine is selected from the group consisting of TNF-RI, TNF-RII, IL-1ra, IL-4, IL-10, IL-12, IL-13, TGF-β

.

36. The method of claim 35, wherein the anti-inflammatory cytokine is TNF-RI.

37. The method of claim 35, wherein the anti-inflammatory cytokine is TNF-RII.

38. The method of claim 35, wherein the anti-inflammatory cytokine is IL-1ra.

39. The method of claim 35, wherein the anti-inflammatory cytokine is IL-4.

40. The method of claim 35, wherein the anti-inflammatory cytokine is IL-10.

41. The method of claim 35, wherein the anti-inflammatory cytokine is IL-12.

42. The method of claim 35, wherein the anti-inflammatory cytokine is IL-13.

43. The method of claim 35, wherein the anti-inflammatory cytokine is TGF-β

.

44. The method of claim 1, wherein the level of at least one inflammatory cytokine is decreased.

45. The method of claim 44, wherein the inflammatory cytokine is a proinflammatory cytokine.

46. The method of claim 45, wherein the proinflammatory cytokine is selected from the group consisting of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, lipopolysaccharide-biding protein, MCP-1, CD-14, GM-CSF, G-CSF and a chemokine.

47. The method of claim 46, wherein the proinflammatory cytokine is TNF-α

.

48. The method of claim 46, wherein the proinflammatory cytokine is IL-1.

49. The method of claim 46, wherein the proinflammatory cytokine is IL-1β

.

50. The method of claim 46, wherein the proinflammatory cytokine is IL-6.

51. The method of claim 46, wherein the proinflammatory cytokine is IL-8.

52. The method of claim 46, wherein the proinflammatory cytokine is lipopolysaccharide-biding protein.

53. The method of claim 46, wherein the proinflammatory cytokine is MCP-1.

54. The method of claim 46, wherein the proinflammatory cytokine is CD-14.

55. The method of claim 46, wherein the proinflammatory cytokine is GM-CSF.

56. The method of claim 46, wherein the proinflammatory cytokine is G-CSF.

57. The method of claim 46, wherein the proinflammatory cytokine is a chemokine.

58. The method of claim 44, wherein the inflammatory cytokine is an anti-inflammatory cytokine.

59. The method of claim 58, wherein the anti-inflammatory cytokine is selected from the group consisting of TNF-RI, TNF-RII, IL-1ra, IL-4, IL-10, IL-12, IL-13, TGF-β

.

60. The method of claim 59, wherein the anti-inflammatory cytokine is TNF-RI.

61. The method of claim 59, wherein the anti-inflammatory cytokine is TNF-RII.

62. The method of claim 59, wherein the anti-inflammatory cytokine is IL-1ra.

63. The method of claim 59, wherein the anti-inflammatory cytokine is IL-4.

64. The method of claim 59, wherein the anti-inflammatory cytokine is IL-10.

65. The method of claim 59, wherein the anti-inflammatory cytokine is IL-12.

66. The method of claim 59, wherein the anti-inflammatory cytokine is IL-13.

67. The method of claim 59, wherein the anti-inflammatory cytokine is TGF-β

.

68. A method of modulating the levels of at least one inflammatory cytokine in a patient in need thereof, comprising:

removing a portion of body fluid from the patient,

contacting the removed body fluid with renal tubule cells, and

returning at least a portion of the body fluid which has been contacted with the renal tubule cells to the patient.

69. The method of claim 68, wherein the patient in need thereof is suffering from one or more disease selected from the group consisting of end-stage renal disease, chronic renal insufficiency, acute renal failure, sepsis, malnutrition, chronic congestive heart failure, inflammatory bowel disease, Crohn'"'"'s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, systemic vasculitis, lupus, Wegener'"'"'s granulomatosis, polyarteritis nodosa, dermatomyositis, diabetes mellitus Type I, thyroiditis, psoriasis, Guillian Barre syndrome, multiple sclerosis, and atherosclerosis, or other autoimmune disorders.

70. The method of claim 69, wherein the patient in need thereof is suffering from one or more disease selected from the group consisting of end-stage renal disease, chronic renal insufficiency, acute renal failure, and sepsis.

71. The method of claim 69, wherein the patient in need thereof is suffering from one or more disease selected from the group consisting malnutrition, chronic congestive heart failure, inflammatory bowel disease, Crohn'"'"'s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, systemic vasculitis, lupus, Wegener'"'"'s granulomatosis, polyarteritis nodosa, dermatomyositis, diabetes mellitus Type I, thyroiditis, psoriasis, Guillian Barre syndrome, multiple sclerosis, and atherosclerosis, or other autoimmune disorders.

72. The method of claim 69, wherein the patient in need thereof is suffering from one or more disease selected from inflammatory bowel disease, Crohn'"'"'s disease, and ulcerative colitis.

73. The method of claim 69, wherein the patient in need thereof is suffering from one or more disease selected from rheumatoid arthritis and ankylosing spondylitis.

74. The method of claim 69, wherein the patient in need thereof is suffering from one or more disease selected from systemic vasculitis, lupus, Wegener'"'"'s granulomatosis, polyarteritis nodosa, and dermatomyositis.

75. The method of claim 69, wherein the patient in need thereof is suffering from one or more disease selected from Guillian Barre syndrome and multiple sclerosis.

76. The method of claim 68, wherein the patient is not afflicted with renal disease.

77. The method of claim 68, wherein the patient is on hemodialysis or peritoneal dialysis.

78. The method of claim 68, wherein the body fluid is blood.

79. The method of claim 68, wherein the body fluid is plasma.

80. The method of claim 68, wherein the body fluid is ultrafiltrate of plasma.

81. The method of claim 68, wherein the body fluid is contacted with the renal tubule cells ex vivo.

82. The method of claim 68, wherein the body fluid is contacted with the renal tubule cells inside the body of the patient.

83. The method of claim 68, wherein the body fluid is contacted with the renal tubule cells in a renal tubule assist device.

84. The method of claim 83, wherein the renal tubule assist device is ex vivo.

85. The method of claim 83, wherein the renal tubule assist device is implanted in the patient.

86. The method of claim 85, wherein the renal tubule cells are in a cell cartridge implanted in a blood vessel of the patient.

87. The method of claim 68, wherein the level of at least one inflammatory cytokine is increased.

88. The method of claim 87, wherein the inflammatory cytokine is a proinflammatory cytokine.

89. The method of claim 88, wherein the proinflammatory cytokine is selected from the group consisting of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, lipopolysaccharide-biding protein, MCP-1, CD-14, GM-CSF, G-CSF and a chemokine.

90. The method of claim 89, wherein the proinflammatory cytokine is TNF-α

.

91. The method of claim 89, wherein the proinflammatory cytokine is IL-1.

92. The method of claim 89, wherein the proinflammatory cytokine is IL-1β

.

93. The method of claim 89, wherein the proinflammatory cytokine is IL-6.

94. The method of claim 89, wherein the proinflammatory cytokine is IL-8.

95. The method of claim 89, wherein the proinflammatory cytokine is lipopolysaccharide-biding protein.

96. The method of claim 89, wherein the proinflammatory cytokine is MCP-1.

97. The method of claim 89, wherein the proinflammatory cytokine is CD-14.

98. The method of claim 89, wherein the proinflammatory cytokine is GM-CSF.

99. The method of claim 89, wherein the proinflammatory cytokine is G-CSF.

100. The method of claim 89, wherein the proinflammatory cytokine is a chemokine.

101. The method of claim 87, wherein the inflammatory cytokine is an anti-inflammatory cytokine.

102. The method of claim 101, wherein the anti-inflammatory cytokine is selected from the group consisting of TNF-RI, TNF-RII, IL-1ra, IL-4, IL-10, IL-12, IL-13, TGF-β

.

103. The method of claim 102, wherein the anti-inflammatory cytokine is TNF-RI.

104. The method of claim 102, wherein the anti-inflammatory cytokine is TNF-RII.

105. The method of claim 102, wherein the anti-inflammatory cytokine is IL-1ra.

106. The method of claim 102, wherein the anti-inflammatory cytokine is IL-4.

107. The method of claim 102, wherein the anti-inflammatory cytokine is IL-10.

108. The method of claim 102, wherein the anti-inflammatory cytokine is IL-12.

109. The method of claim 102, wherein the anti-inflammatory cytokine is IL-13.

110. The method of claim 102, wherein the anti-inflammatory cytokine is TGF-β

.

111. The method of claim 68, wherein the level of at least one inflammatory cytokine is decreased.

112. The method of claim 111, wherein the inflammatory cytokine is a proinflammatory cytokine.

113. The method of claim 112, wherein the proinflammatory cytokine is selected from the group consisting of TNF-α

, IL-1, IL-1β

, IL-6, IL-8, lipopolysaccharide-biding protein, MCP-1, CD-14, GM-CSF, G-CSF and a chemokine.

114. The method of claim 113, wherein the proinflammatory cytokine is TNF-α

.

115. The method of claim 113, wherein the proinflammatory cytokine is IL-1.

116. The method of claim 113, wherein the proinflammatory cytokine is IL-1β

.

117. The method of claim 113, wherein the proinflammatory cytokine is IL-6.

118. The method of claim 113, wherein the proinflammatory cytokine is IL-8.

119. The method of claim 113, wherein the proinflammatory cytokine is lipopolysaccharide-biding protein.

120. The method of claim 113, wherein the proinflammatory cytokine is MCP-1.

121. The method of claim 113, wherein the proinflammatory cytokine is CD-14.

122. The method of claim 113, wherein the proinflammatory cytokine is GM-CSF.

123. The method of claim 113, wherein the proinflammatory cytokine is G-CSF.

124. The method of claim 113, wherein the proinflammatory cytokine is a chemokine.

125. The method of claim 111, wherein the inflammatory cytokine is an anti-inflammatory cytokine.

126. The method of claim 125, wherein the anti-inflammatory cytokine is selected from the group consisting of TNF-RI, TNF-RII, IL-1ra, IL-4, IL-10, IL-12, IL-13, TGF-β

.

127. The method of claim 126, wherein the anti-inflammatory cytokine is TNF-RI.

128. The method of claim 126, wherein the anti-inflammatory cytokine is TNF-RII.

129. The method of claim 126, wherein the anti-inflammatory cytokine is IL-1ra.

130. The method of claim 126, wherein the anti-inflammatory cytokine is IL-4.

131. The method of claim 126, wherein the anti-inflammatory cytokine is IL-10.

132. The method of claim 126, wherein the anti-inflammatory cytokine is IL-12.

133. The method of claim 126, wherein the anti-inflammatory cytokine is IL-13.

134. The method of claim 126, wherein the anti-inflammatory cytokine is TGF-β

.