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Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease

Ridker, Paul M., Rane, Manas·2021·Circulation Research
DOI 10.1161/circresaha.121.319077
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Abstract

IL (interleukin)-6 is a pivotal cytokine of innate immunity, which enacts a broad set of physiological functions traditionally associated with host defense, immune cell regulation, proliferation, and differentiation. Following recognition of innate immune pathways leading from the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome to IL-1 to IL-6 and on to the hepatically derived clinical biomarker CRP (C-reactive protein), an expanding literature has led to understanding of the proatherogenic role for IL-6 in cardiovascular disease and thus the potential for IL-6 inhibition as a novel method for vascular protection. In this review, we provide an overview of the mechanisms by which IL-6 signaling occurs and how that impacts upon pharmacological inhibition; describe murine models of IL-6 and atherogenesis; summarize human epidemiological data outlining the utility of IL-6 as a biomarker of vascular risk; outline genetic data suggesting a causal role for IL-6 in systemic atherothrombosis and aneurysm formation; and then detail the potential role of IL-6 inhibition in stable coronary disease, acute coronary syndromes, heart failure, and the atherothrombotic complications associated with chronic kidney disease and end-stage renal failure. Finally, we review anti-inflammatory and antithrombotic findings for ziltivekimab, a novel IL-6 ligand inhibitor being developed specifically for use in atherosclerotic disease and poised to be tested formally in a large-scale cardiovascular outcomes trial focused on individuals with chronic kidney disease and elevated levels of CRP, a population at high residual atherothrombotic risk, high residual inflammatory risk, and considerable unmet clinical need.

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Research works printed but not linked: 145

  1. 10.1097/MNH.0b013e32834ad504 · DOI
  2. 10.1007/s11883-017-0660-3 · DOI
  3. 10.1161/CIRCRESAHA.115.306656 · DOI · Paper page
  4. 10.1093/eurheartj/ehz283 · DOI · Paper page
  5. 10.1056/NEJMoa1707914 · DOI · Paper page
  6. 10.1093/eurheartj/ehy310 · DOI · Paper page
  7. 10.1097/CRD.0000000000000021 · DOI
  8. 10.1016/j.ijcard.2018.02.062 · DOI
  9. 10.1016/j.jacc.2021.02.060 · DOI
  10. 10.1016/0008-8749(89)90095-6 · DOI
  11. 10.1172/JCI114498 · DOI
  12. 10.1038/nrd.2018.45 · DOI · Paper page
  13. 10.1038/ni.3632 · DOI · Paper page
  14. Poli, V, Maritano, D. IL-6 deficient mice. Fantuzzi, G ed. In: Cytokine Knockouts. Contemporary Immunology. Humana Press; 2003:213–235. · DOI
  15. 10.1016/s0021-9150(99)00463-3 · DOI · Paper page
  16. 10.2174/157340308785160570 · DOI
  17. 10.1016/j.atherosclerosis.2006.10.013 · DOI
  18. 10.1161/01.atv.17.12.3399 · DOI
  19. 10.1016/s1074-7613(00)80334-9 · DOI
  20. 10.1152/ajpcell.00235.2017 · DOI
  21. 10.1161/01.atv.19.10.2364 · DOI · Paper page
  22. 10.1161/ATVBAHA.111.229435 · DOI
  23. 10.1016/j.abb.2012.09.007 · DOI
  24. 10.1161/01.CIR.0000148135.08582.97 · DOI · Paper page
  25. 10.1160/TH09-05-0297 · DOI
  26. 10.1371/journal.pone.0187189 · DOI
  27. 10.1093/cvr/cvq078 · DOI
  28. 10.3389/fcvm.2017.00084 · DOI
  29. 10.1371/journal.pone.0167195 · DOI
  30. 10.1096/fj.03-0331fje · DOI
  31. 10.1056/NEJM199704033361401 · DOI · Paper page
  32. 10.1161/01.cir.101.15.1767 · DOI · Paper page
  33. 10.1016/S0140-6736(09)61717-7 · DOI · Paper page
  34. 10.1093/eurheartj/eht367 · DOI
  35. 10.1001/jama.286.3.327 · DOI · Paper page
  36. 10.1161/01.cir.0000055014.62083.05 · DOI · Paper page
  37. 10.1001/jama.290.22.2945 · DOI
  38. 10.1016/s0002-9343(99)00066-2 · DOI · Paper page
  39. 10.1373/clinchem.2008.120642 · DOI
  40. 10.1161/JAHA.114.001084 · DOI
  41. 10.1161/CIRCRESAHA.114.302770 · DOI
  42. 10.1056/NEJM199408183310701 · DOI
  43. 10.1056/NEJM200010193431602 · DOI
  44. 10.1161/JAHA.116.005077 · DOI
  45. 10.1161/JAHA.117.005637 · DOI
  46. 10.1161/01.CIR.0000158479.58589.0A · DOI
  47. 10.1016/j.ijcard.2006.09.004 · DOI
  48. 10.1161/JAHA.115.003014 · DOI
  49. 10.1093/eurheartj/ehaa160 · DOI
  50. 10.1016/j.ajhg.2008.03.015 · DOI
  51. 10.1016/j.ajhg.2012.07.023 · DOI
  52. 10.1161/CIRCULATIONAHA.110.948570 · DOI
  53. 10.1161/CIRCRESAHA.117.312086 · DOI · Paper page
  54. 10.1038/s41525-019-0097-4 · DOI
  55. 10.1001/jamacardio.2018.2287 · DOI
  56. 10.1161/CIRCULATIONAHA.119.044362 · DOI · Paper page
  57. 10.1016/S0140-6736(17)32814-3 · DOI
  58. 10.1093/eurheartj/ehz542 · DOI
  59. 10.1016/S0140-6736(17)32247-X · DOI · Paper page
  60. 10.7326/M18-1167 · DOI
  61. 10.7326/M19-2945 · DOI
  62. 10.7326/M20-0527 · DOI
  63. 10.1161/CIRCULATIONAHA.120.050560 · DOI · Paper page
  64. 10.1016/j.cjca.2020.10.006 · DOI
  65. 10.1016/j.jacc.2014.01.014 · DOI
  66. 10.1093/eurheartj/ehu272 · DOI
  67. 10.1093/eurheartj/ehw171 · DOI
  68. 10.1161/JAHA.119.015628 · DOI
  69. 10.1161/CIRCINTERVENTIONS.119.008717 · DOI
  70. 10.1016/j.jacc.2013.03.003 · DOI
  71. 10.1001/jama.286.17.2107 · DOI
  72. 10.1161/JAHA.119.014941 · DOI
  73. 10.1007/s00392-018-1387-z · DOI
  74. 10.1016/j.jacc.2021.02.049 · DOI
  75. 10.1016/j.jacc.2020.08.052 · DOI
  76. 10.1093/eurheartj/ehw247 · DOI
  77. 10.1001/jama.2016.3609 · DOI · Paper page
  78. 10.1016/s0735-1097(96)00268-9 · DOI
  79. 10.1016/j.cardiores.2005.08.017 · DOI
  80. 10.1016/s0735-1097(97)00494-4 · DOI
  81. 10.1016/s0735-1097(00)00912-8 · DOI
  82. 10.1161/01.cir.0000057810.48709.f6 · DOI
  83. 10.2174/1573403x12666160111125304 · DOI
  84. 10.1016/s1388-9842(01)00137-4 · DOI
  85. 10.1016/j.jacc.2009.12.045 · DOI · Paper page
  86. 10.1002/ejhf.1482 · DOI
  87. 10.1172/JCI20945 · DOI · Paper page
  88. 10.1161/01.CIR.0000077913.60364.D2 · DOI · Paper page
  89. 10.1161/01.CIR.0000124490.27666.B2 · DOI · Paper page
  90. 10.1371/journal.pone.0033438 · DOI
  91. 10.1161/CIRCHEARTFAILURE.117.004373 · DOI
  92. 10.1161/CIRCRESAHA.116.302317 · DOI
  93. 10.1073/pnas.1108586108 · DOI
  94. 10.1016/j.jacc.2017.12.037 · DOI · Paper page
  95. 10.1161/CIRCULATIONAHA.118.038010 · DOI · Paper page
  96. 10.1002/ejhf.963 · DOI
  97. 10.1161/CIRCULATIONAHA.109.849117 · DOI
  98. 10.1038/ki.2011.178 · DOI
  99. 10.1097/01.mnh.0000444814.49755.90 · DOI
  100. 10.1111/nep.12785 · DOI
  101. 10.1038/ki.2009.503 · DOI
  102. 10.1016/s0272-6386(00)70200-9 · DOI
  103. 10.1093/ndt/17.9.1684 · DOI
  104. 10.2215/CJN.03500412 · DOI
  105. 10.1053/j.ajkd.2018.09.012 · DOI
  106. 10.1016/j.jdiacomp.2016.07.018 · DOI
  107. 10.1038/labinvest.2014.163 · DOI
  108. 10.1016/j.kint.2017.09.011 · DOI
  109. 10.1093/ndt/gfw360 · DOI
  110. 10.1182/blood.V83.9.2570.2570 · DOI
  111. 10.1161/HYPERTENSIONAHA.111.173328 · DOI
  112. 10.1016/s0272-6386(97)90495-9 · DOI
  113. 10.1681/ASN.2005040393 · DOI
  114. 10.1053/j.ackd.2017.12.002 · DOI
  115. 10.1053/j.ajkd.2009.12.030 · DOI
  116. 10.2215/CJN.00380111 · DOI
  117. 10.2215/CJN.07000714 · DOI
  118. 10.3389/fimmu.2017.00405 · DOI
  119. 10.1111/j.1523-1755.2002.kid556.x · DOI
  120. 10.1053/j.ajkd.2009.06.029 · DOI
  121. 10.2215/CJN.10441015 · DOI
  122. 10.1681/ASN.2010070760 · DOI
  123. 10.1007/s40620-014-0070-3 · DOI
  124. 10.1097/MNH.0000000000000079 · DOI
  125. 10.1080/13543784.2016.1196184 · DOI
  126. 10.1093/ndt/gfx377 · DOI
  127. 10.1016/j.jacc.2018.03.490 · DOI
  128. 10.1177/089686080602600109 · DOI
  129. 10.1093/ndt/gfu233 · DOI
  130. 10.1681/ASN.2020050595 · DOI
  131. 10.1016/j.imbio.2004.09.006 · DOI
  132. 10.1093/eurheartj/ehaa1049 · DOI
  133. 10.1016/j.atherosclerosis.2011.09.015 · DOI
  134. 10.1161/JAHA.116.005038 · DOI
  135. 10.1136/annrheumdis-2013-204345 · DOI
  136. 10.1007/s00296-009-1303-y · DOI
  137. 10.1016/j.atherosclerosis.2013.04.031 · DOI
  138. 10.1002/art.41095 · DOI
  139. 10.1136/annrheumdis-2014-205675 · DOI · Paper page
  140. 10.2174/138161282004140213123852 · DOI
  141. 10.3389/fimmu.2018.01234 · DOI
  142. 10.1136/annrheumdis-2017-211555 · DOI
  143. 10.1038/nrrheum.2017.23 · DOI
  144. 10.1016/S0140-6736(21)00520-1 · DOI
  145. 10.1016/j.jacc.2021.02.060 · DOI

Cited by

Metadata

Authors
Ridker, P. M., & Rane, M.
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-05-28
Volume
128
Issue
11
Pages
1728-1746
ISSN
  • 0009-7330
  • 1524-4571
DOI
10.1161/circresaha.121.319077
Cited by
691
References
19
Language
en

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