title: Complement in immune and inflammatory disorders: therapeutic interventions.
abstract: With the awareness that immune-inflammatory cross-talk is at the heart of many disorders, the desire for novel immunomodulatory strategies in the therapy of such diseases has grown dramatically. As a prime initiator and important modulator of immunological and inflammatory processes, the complement system has emerged as an attractive target for early and upstream intervention in inflammatory diseases and has moved into the spotlight of drug discovery. Although prevalent conditions such as age-related macular degeneration have attracted the most attention, the diverse array of complement-mediated pathologies, with distinct underlying mechanisms, demands a multifaceted arsenal of therapeutic strategies. Fortunately, efforts in recent years have not only introduced the first complement inhibitors to the clinic but also filled the pipelines with promising candidates. With a focus on immunomodulatory strategies, in this review we discuss complement-directed therapeutic concepts and highlight promising candidate molecules.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ricklin@upenn.edu
authors.forename: Daniel
authors.initials: D
authors.lastname: Ricklin
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
mesh_terms: D000818:Animals; D003170:Complement Pathway, Alternative / Q000276:immunology; D003171:Complement Pathway, Classical / Q000276:immunology; D003165:Complement System Proteins / Q000502:physiology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D055808:Drug Discovery; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use
chemical_list: D007155:Immunologic Factors; D018836:Inflammation Mediators; D003165:Complement System Proteins
references.citation: Adv Exp Med Biol. 2010;703:151-62
references.pmid: 20711713
references.citation: J Biol Chem. 2012 Apr 13;287(16):12886-92
references.pmid: 22362762
references.citation: Mol Cell Probes. 1987 Jun;1(2):141-9
references.pmid: 3453897
references.citation: Int J Hematol. 2011 Jun;93(6):704-714
references.pmid: 21611719
references.citation: J Immunol. 2007 Feb 1;178(3):1783-90
references.pmid: 17237428
references.citation: PLoS One. 2011 Apr 28;6(4):e19078
references.pmid: 21552568
references.citation: J Thorac Cardiovasc Surg. 2011 Jul;142(1):89-98
references.pmid: 20880552
references.citation: Mol Immunol. 2011 Aug;48(14):1643-55
references.pmid: 21624663
references.citation: Kidney Int. 2010 Jul;78(2):152-9
references.pmid: 20336054
references.citation: J Clin Invest. 1995 Sep;96(3):1564-72
references.pmid: 7657827
references.citation: J Immunol. 2013 Apr 15;190(8):3831-8
references.pmid: 23564577
references.citation: J Innate Immun. 2010;2(1):87-92
references.pmid: 20375626
references.citation: Transplantation. 2010 Dec 27;90(12):1358-65
references.pmid: 21197712
references.citation: Blood. 2012 Jun 28;119(26):6307-16
references.pmid: 22577173
references.citation: Adv Exp Med Biol. 2013;735:1-22
references.pmid: 22990692
references.citation: Blood. 2005 Oct 1;106(7):2559-65
references.pmid: 15985537
references.citation: Am J Transplant. 2011 Oct;11(10):2057-66
references.pmid: 21831160
references.citation: Adv Exp Med Biol. 2013;735:247-55
references.pmid: 23402032
references.citation: EMBO Mol Med. 2011 Nov;3(11):617-9
references.pmid: 21954211
references.citation: JAMA. 2004 May 19;291(19):2319-27
references.pmid: 15150203
references.citation: Blood. 2010 Jul 29;116(4):631-9
references.pmid: 20424189
references.citation: Mol Immunol. 2011 Aug;48(14):1631-42
references.pmid: 21549429
references.citation: J Periodontal Res. 2011 Dec;46(6):643-7
references.pmid: 21722134
references.citation: BMC Cardiovasc Disord. 2010 Sep 27;10:45
references.pmid: 20875134
references.citation: Nat Med. 2011 Nov 06;17(12):1674-9
references.pmid: 22057346
references.citation: Am J Kidney Dis. 2013 Feb;61(2):289-99
references.pmid: 23141475
references.citation: Immunobiology. 2012 Nov;217(11):1047-56
references.pmid: 22964230
references.citation: J Immunol. 2011 Apr 1;186(7):4269-77
references.pmid: 21339361
references.citation: Mol Immunol. 2005 Jan;42(1):87-97
references.pmid: 15488947
references.citation: J Exp Med. 2003 Sep 15;198(6):913-23
references.pmid: 12975457
references.citation: Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):E415-22
references.pmid: 22308431
references.citation: J Thorac Cardiovasc Surg. 2008 Oct;136(4):884-93
references.pmid: 18954626
references.citation: Semin Thromb Hemost. 2011 Jun;37(4):362-74
references.pmid: 21805442
references.citation: Biochem Soc Trans. 2002 Nov;30(Pt 6):1037-41
references.pmid: 12440967
references.citation: Immunobiology. 2013 Apr;218(4):496-505
references.pmid: 22795972
references.citation: Circulation. 2012 Oct 30;126(18):2227-35
references.pmid: 23032324
references.citation: Nat Rev Drug Discov. 2004 Sep;3(9):797-801
references.pmid: 15340389
references.citation: Arthritis Rheum. 2012 Aug;64(8):2559-67
references.pmid: 22334275
references.citation: Blood. 2010 Mar 18;115(11):2283-91
references.pmid: 20068220
references.citation: Am J Pathol. 2007 Sep;171(3):715-27
references.pmid: 17640961
references.citation: Immunobiology. 2012 Nov;217(11):1080-7
references.pmid: 22964233
references.citation: J Clin Invest. 2010 Oct;120(10):3545-54
references.pmid: 20941861
references.citation: J Immunol. 2009 Jul 15;183(2):1375-83
references.pmid: 19561098
references.citation: Immunobiology. 2010 May;215(5):395-405
references.pmid: 19586684
references.citation: Adv Exp Med Biol. 2013;735:137-54
references.pmid: 23402024
references.citation: Adv Exp Med Biol. 2010;703:127-35
references.pmid: 20711711
references.citation: Bioorg Med Chem Lett. 2006 Apr 15;16(8):2200-4
references.pmid: 16460935
references.citation: Brain Res. 2009 Nov 17;1298:171-7
references.pmid: 19410563
references.citation: Mol Immunol. 2009 Dec;47(2-3):185-95
references.pmid: 19800693
references.citation: Nat Med. 2012 Sep;18(9):1340-1
references.pmid: 22961162
references.citation: Nat Rev Microbiol. 2008 Feb;6(2):132-42
references.pmid: 18197169
references.citation: Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8955-9
references.pmid: 7568051
references.citation: Curr Opin Mol Ther. 2006 Dec;8(6):529-38
references.pmid: 17243489
references.citation: Blood. 2011 Oct 27;118(17):4705-13
references.pmid: 21860027
references.citation: Br J Pharmacol. 2013 Jan;168(2):488-501
references.pmid: 22924972
references.citation: Curr Opin Investig Drugs. 2001 Mar;2(3):364-71
references.pmid: 11575706
references.citation: Vaccine. 2009 Dec 11;28(2):463-9
references.pmid: 19836478
references.citation: Expert Rev Anti Infect Ther. 2012 Mar;10(3):249-51
references.pmid: 22397555
references.citation: Immunol Lett. 2005 Sep 15;100(2):139-45
references.pmid: 16154494
references.citation: Scand J Immunol. 2009 Jun;69(6):471-8
references.pmid: 19439007
references.citation: FASEB J. 2013 Feb;27(2):822-31
references.pmid: 23118029
references.citation: Bioorg Med Chem Lett. 2012 Aug 15;22(16):5303-7
references.pmid: 22795627
references.citation: Immunobiology. 2012 Nov;217(11):1057-66
references.pmid: 22964231
references.citation: J Biol Chem. 2009 Apr 17;284(16):10473-9
references.pmid: 19196712
references.citation: Cell Microbiol. 2010 Oct;12(10):1506-16
references.pmid: 20545943
references.citation: Biomaterials. 2013 Jan;34(4):985-94
references.pmid: 23137394
references.citation: Vaccine. 2011 Dec 9;30(1):9-13
references.pmid: 22044742
references.citation: Blood. 2010 Aug 12;116(6):1002-10
references.pmid: 20466856
references.citation: Nat Med. 2012 Sep;18(9):1401-6
references.pmid: 22922409
references.citation: J Biol Chem. 2007 Mar 16;282(11):8292-9
references.pmid: 17215252
references.citation: Adv Exp Med Biol. 2013;735:123-36
references.pmid: 23402023
references.citation: J Clin Invest. 2005 Sep;115(9):2444-53
references.pmid: 16127466
references.citation: Scand J Immunol. 2006 Mar;63(3):155-68
references.pmid: 16499568
references.citation: J Immunol. 2011 Nov 1;187(9):4913-9
references.pmid: 21964028
references.citation: Toxicon. 2010 Dec 15;56(7):1198-222
references.pmid: 20417224
references.citation: Proc Natl Acad Sci U S A. 2011 May 3;108(18):7523-8
references.pmid: 21502512
references.citation: Immunobiology. 2012 Jul;217(7):698-703
references.pmid: 22206707
references.citation: Clin Exp Immunol. 2004 Dec;138(3):439-46
references.pmid: 15544620
references.citation: Cardiovasc Pathol. 2013 Jan-Feb;22(1):75-80
references.pmid: 22705194
references.citation: Rheumatology (Oxford). 2007 Dec;46(12):1773-8
references.pmid: 17965442
references.citation: J Ocul Pharmacol Ther. 2012 Aug;28(4):402-9
references.pmid: 22309197
references.citation: J Biol Chem. 2012 Jun 8;287(24):20290-300
references.pmid: 22511776
references.citation: PLoS One. 2007 Jul 18;2(7):e623
references.pmid: 17637839
references.citation: Nat Med. 1999 Jul;5(7):788-92
references.pmid: 10395324
references.citation: Expert Rev Cardiovasc Ther. 2006 Sep;4(5):649-54
references.pmid: 17081086
references.citation: Transplantation. 2008 Nov 27;86(10):1445-51
references.pmid: 19034016