title: Distinct effects of anti-tumor necrosis factor combined therapy on TH1/TH2 balance in rheumatoid arthritis patients.
abstract: The immune balance in patients with rheumatoid arthritis (RA), a disease characterized by TH1 dominance, treated by the preferred combined anti-tumor necrosis factor (anti-TNF) and methotrexate (MTX) therapy was evaluated by assessing the chemokine and cytokine receptors as well as apoptosis induction. A meta-analysis of combined therapy by TNF blockers and MTX in 15 RA patients, MTX monotherapy in 20 RA patients, and 11 diagnosed but untreated RA patients was performed by assessing several immune markers in the whole lymphocyte population, as well as in specific CD4 cells, by both flow cytometry and image analysis. A significant downregulation of CXCR3 and IL-12 receptors (both TH1 markers) and a significant increase in the chemokine receptor CCR4 and, to a lesser extent, IL-4R (both TH2 markers) were found; a particularly marked increase was found in patients treated by combined therapy. This phenomenon was pronounced in CD4 cells and was accompanied by a high proportion of apoptotic cells. The therapeutic effect of MTX and TNF blockers may be due to apoptosis induction in lymphocytes infiltrating from the inflammation site and restoring the TH1/TH2 balance.
authors: The Biophysical Interdisciplinary Schottenstein Center for the Research and the Technology of the Cellome, Physics Department, Bar Ilan University, Ramat Gan 52900, Israel.
authors: S
authors: S
authors: Herman
authors: N
authors: N
authors: Zurgil
authors: S
authors: S
authors: Machlav
authors: A
authors: A
authors: Shinberg
authors: P
authors: P
authors: Langevitz
authors: M
authors: M
authors: Ehrenfeld
authors: M
authors: M
authors: Deutsch
references: BioDrugs. 2004;18(2):121-39
references: 15046527
references: J Rheumatol. 2004 Nov;31(11):2189-98
references: 15517632
references: Ann Rheum Dis. 2000 Apr;59(4):263-8
references: 10733472
references: Clin Exp Immunol. 2004 Nov;138(2):342-7
references: 15498047
references: Nephrol Dial Transplant. 2004 Dec;19(12):3084-90
references: 15574999
references: Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G612-20
references: 19136378
references: Pharmacol Rev. 2005 Jun;57(2):163-72
references: 15914465
references: J Clin Invest. 1998 Jul 15;102(2):322-8
references: 9664073
references: Arthritis Rheum. 1988 Mar;31(3):315-24
references: 3358796
references: J Clin Rheumatol. 2005 Jun;11(3 Suppl):S55-62
references: 16357751
references: Arthritis Res Ther. 2005;7(3):R493-502
references: 15899036
references: Immunol Invest. 2004 Aug;33(3):351-62
references: 15495793
references: N Engl J Med. 2000 Nov 30;343(22):1594-602
references: 11096166
references: Rheumatology (Oxford). 2004 Jun;43 Suppl 3:iii17-iii23
references: 15150428
references: Cell Struct Funct. 2003 Apr;28(2):113-22
references: 12808231
references: Semin Arthritis Rheum. 2001 Dec;31(3):160-75
references: 11740797
references: Arch Immunol Ther Exp (Warsz). 2000;48(5):429-35
references: 11140470
references: Drugs. 2004;64(12):1267-83
references: 15200343
references: Clin Exp Rheumatol. 2008 Mar-Apr;26(2):317-23
references: 18565255
references: J Clin Rheumatol. 2005 Jun;11(3 Suppl):S39-44
references: 16357749
references: Clin Exp Immunol. 1999 Oct;118(1):137-46
references: 10540171
references: Rinsho Byori. 2008 Apr;56(4):309-15
references: 18516965
references: Biochem J. 1999 Aug 15;342 ( Pt 1):143-52
references: 10432311
references: Aliment Pharmacol Ther. 2005 Feb 1;21(3):251-8
references: 15691299
references: Lancet. 2004 Feb 28;363(9410):675-81
references: 15001324
references: Arthritis Rheum. 1995 Jan;38(1):44-8
references: 7818570
references: Annu Rev Med. 2000;51:207-29
references: 10774461
references: Blood. 1999 Feb 15;93(4):1145-56
references: 9949156
references: J Rheumatol Suppl. 2005 Mar;74:31-4
references: 15742462
references: Rheumatol Int. 2008 Apr;28(6):553-9
references: 17943257
references: Am J Pathol. 2002 Jan;160(1):347-55
references: 11786428