title: Protective effect of eotaxin-2 inhibition in adjuvant-induced arthritis.
abstract: Eotaxin-2 is a potent chemoattractant for eosinophils, basophils and T helper type 2 (Th2) lymphocytes. The eotaxin-2/CCL24 receptor CCR3 is expressed in human brain, skin, endothelium and macrophages. The aim of the current study was to evaluate the protective effect of a monoclonal anti-eotaxin-2 antibody on the development of adjuvant-induced arthritis in rats (AIA). Adjuvant arthritis was induced in Lewis rats by intradermal injection of incomplete Freund's adjuvant +Mycobacterium tuberculosis. Rats were treated by intraperitoneal (i.p.) injection with three monoclonal antibodies against eotaxin-2 (G7, G8, D8) three times per week. Controls were treated with total mouse immunoglobulin G (IgG), methotrexate (MTX) or phosphate-buffered saline (PBS). Arthritis severity was evaluated by measuring ankle swelling, arthritic score, whole animal mobility and body weight. Sample joints were obtained for pathological evaluation and postmortem X-ray of ankle joints was performed to document erosions. Significant inhibition of arthritis was observed in rats treated with anti-eotaxin-2 antibodies compared to those treated with immunoglobulin or PBS. Inhibition was manifest in ankle diameter, arthritic score and mobility score. The antibody marked D8 showed the greatest efficacy. The effect was observed both in animals treated before the appearance of arthritis and in those where treatment was begun after development of joint inflammation. Combined treatment with D8 and MTX caused additional protection. Significant reduction of inflammation in D8-treated animals was also demonstrated in pathological and X-ray examinations. Inhibition of eotaxin-2 by monoclonal antibodies has a significant protective effect in adjuvant arthritis. These results may introduce a novel therapeutic target in rheumatoid arthritis and additional inflammatory joint disorders.
authors.affiliation: Sourasky Medical Center, Rheumatology Institute, Tel-Aviv University, Tel-Aviv, Israel. ajacob@post.tau.ac.il
authors.forename: J N
authors.initials: JN
authors.lastname: Ablin
authors.forename: M
authors.initials: M
authors.lastname: Entin-Meer
authors.forename: V
authors.initials: V
authors.lastname: Aloush
authors.forename: S
authors.initials: S
authors.lastname: Oren
authors.forename: O
authors.initials: O
authors.lastname: Elkayam
authors.forename: J
authors.initials: J
authors.lastname: George
authors.forename: I
authors.initials: I
authors.lastname: Barshack
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D001175:Arthrography; D001835:Body Weight / Q000187:drug effects; D054423:Chemokine CCL24 / Q000037:antagonists & inhibitors* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D013643:Tarsus, Animal / Q000187:drug effects / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D054423:Chemokine CCL24; D005620:Freund's Adjuvant; D008727:Methotrexate
references.citation: J Clin Invest. 1996 Feb 1;97(3):604-12
references.pmid: 8609214
references.citation: J Exp Med. 1998 Mar 16;187(6):875-83
references.pmid: 9500790
references.citation: Annu Rev Pharmacol Toxicol. 2008;48:171-97
references.pmid: 17883327
references.citation: J Neuroimmunol. 2000 Aug 1;108(1-2):192-200
references.pmid: 10900353
references.citation: Inflamm Bowel Dis. 2008 Jul;14(7):1000-11
references.pmid: 18452220
references.citation: J Clin Invest. 2001 Jan;107(1):53-63
references.pmid: 11134180
references.citation: Eur J Immunol. 1998 Jul;28(7):2152-8
references.pmid: 9692884
references.citation: J Immunol. 2002 Sep 15;169(6):2925-36
references.pmid: 12218106
references.citation: J Clin Invest. 1997 Sep 1;100(5):1137-43
references.pmid: 9276730
references.citation: Arthritis Rheum. 2005 Jun;52(6):1907-19
references.pmid: 15934086
references.citation: Curr Allergy Asthma Rep. 2005 Mar;5(2):155-60
references.pmid: 15683617
references.citation: Am J Respir Cell Mol Biol. 2002 Jun;26(6):645-9
references.pmid: 12034562
references.citation: Inflamm Res. 2002 May;51(5):252-8
references.pmid: 12056513
references.citation: Ann Rheum Dis. 2007 May;66(5):589-98
references.pmid: 17170049
references.citation: Am J Pathol. 1999 Oct;155(4):1195-204
references.pmid: 10514402
references.citation: Ann Rheum Dis. 2006 Mar;65(3):294-300
references.pmid: 16107514
references.citation: Nature. 2003 May 15;423(6937):356-61
references.pmid: 12748655
references.citation: Arthritis Rheum. 2001 Feb;45(1):101-6
references.pmid: 11308054
references.citation: J Immunol. 2000 Sep 1;165(5):2748-54
references.pmid: 10946306
references.citation: J Immunol. 1999 Oct 1;163(7):3976-84
references.pmid: 10491000
references.citation: Int J Cancer. 2006 Nov 1;119(9):2026-9
references.pmid: 16671092
references.citation: Arthritis Rheum. 2005 Dec;52(12):3718-30
references.pmid: 16320322
references.citation: J Biol Chem. 1996 Mar 29;271(13):7725-30
references.pmid: 8631813
references.citation: J Clin Invest. 1997 Jan 15;99(2):178-84
references.pmid: 9005985
references.citation: J Biol Chem. 1995 Jul 14;270(28):16491-4
references.pmid: 7622448
references.citation: Ann Rheum Dis. 2007 Jun;66(6):712-9
references.pmid: 16901957
references.citation: Clin Exp Immunol. 1998 Dec;114(3):330-2
references.pmid: 9844039
references.citation: Arthritis Rheum. 2004 Dec;50(12):3866-77
references.pmid: 15593223
references.citation: Allergy. 2002 Jan;57(1):17-22
references.pmid: 11991282
references.citation: EMBO J. 2006 Feb 8;25(3):447-56
references.pmid: 16437164
references.citation: Science. 1997 Sep 26;277(5334):2005-7
references.pmid: 9302298