Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile.
Low back pain is a common and debilitating disorder. Current evidence implicates intervertebral disc (IVD) degeneration and herniation as major causes, although the pathogenesis is poorly understood. While several cytokines have been implicated in the process of IVD degeneration and herniation, investigations have predominately focused on Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFalpha). However, to date no studies have investigated the expression of these cytokines simultaneously in IVD degeneration or herniation, or determined which may be the predominant cytokine associated with these disease states. Using quantitative real time PCR and immunohistochemistry we investigated gene and protein expression for IL-1beta, TNFalpha and their receptors in non-degenerate, degenerate and herniated human IVDs. IL-1beta gene expression was observed in a greater proportion of IVDs than TNFalpha (79% versus 59%). Degenerate and herniated IVDs displayed higher levels of both cytokines than non-degenerate IVDs, although in degenerate IVDs higher levels of IL-1beta gene expression (1,300 copies/100 ng cDNA) were observed compared to those of TNFalpha (250 copies of TNFalpha/100 ng cDNA). Degenerate IVDs showed ten-fold higher IL-1 receptor gene expression compared to non-degenerate IVDs. In addition, 80% of degenerate IVD cells displayed IL-1 receptor immunopositivity compared to only 30% of cells in non-degenerate IVDs. However, no increase in TNF receptor I gene or protein expression was observed in degenerate or herniated IVDs compared to non-degenerate IVDs. We have demonstrated that although both cytokines are produced by human IVD cells, IL-1beta is expressed at higher levels and in more IVDs, particularly in more degenerate IVDs (grades 4 to 12). Importantly, this study has highlighted an increase in gene and protein production for the IL-1 receptor type I but not the TNF receptor type I in degenerate IVDs. The data thus suggest that although both cytokines may be involved in the pathogenesis of IVD degeneration, IL-1 may have a more significant role than TNFalpha, and thus may be a better target for therapeutic intervention.
Le Maitre
Christine Lyn
CL
Tissue Injury and Repair Group, School of Medicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Hoyland
Judith Alison
JA
Freemont
Anthony J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008660:Metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D053583:Interleukin-1beta; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha
Eur Spine J. 2002 Aug;11(4):308-20
12193991
J Pathol. 2002 Jul;197(3):286-92
12115873
Swiss Med Wkly. 2003 Mar 22;133(11-12):170-7
12715286
Int J Clin Pract. 2003 Apr;57(3):231-4
12723729
Rheumatology (Oxford). 2004 Feb;43(2):119-21
13130150
J Pathol. 2004 Sep;204(1):47-54
15307137
Spine (Phila Pa 1976). 1995 Nov 15;20(22):2373-8
8578386
Spine (Phila Pa 1976). 1996 Feb 1;21(3):271-7
8742201
Spine (Phila Pa 1976). 1996 Jan 15;21(2):218-24
8720407
Spine (Phila Pa 1976). 1996 Jan 15;21(2):235-41
8720410
Spine (Phila Pa 1976). 1998 Dec 1;23(23):2538-44
9854752
Spine (Phila Pa 1976). 2004 Nov 15;29(22):2477-84
15543058
Spine (Phila Pa 1976). 2005 Jan 1;30(1):44-53; discussion 54
15626980
Spine (Phila Pa 1976). 2005 Mar 15;30(6):621-4
15770175
Arthritis Res Ther. 2005;7(4):R732-45
15987475
Spine (Phila Pa 1976). 2005 Sep 1;30(17):1940-8
16135983
Int J Exp Pathol. 2006 Feb;87(1):17-28
16436110
Spine (Phila Pa 1976). 2006 Mar 1;31(5):530-5
16508546
Joint Bone Spine. 2006 Mar;73(2):151-8
16046173
Spine (Phila Pa 1976). 2006 Nov 15;31(24):2759-66
17108825
Biotech Histochem. 2006 Jul-Dec;81(4-6):125-31
17129995
Best Pract Res Clin Rheumatol. 2007 Feb;21(1):77-91
17350545
Ann N Y Acad Sci. 2007 Jan;1096:44-54
17405915
Spine (Phila Pa 1976). 2007 Mar 15;32(6):635-42
17413467
Anesthesiology. 2007 Jul;107(1):99-105
17585221
Spine (Phila Pa 1976). 2000 Feb 15;25(4):487-92
10707396
Pain. 2000 Jan;84(1):95-103
10601677
Arthritis Res Ther. 2007;9(3):R45
17498290
Spine (Phila Pa 1976). 2000 Dec 1;25(23):2975-80
11145807
Mol Pathol. 2002 Apr;55(2):91-7
11950957
Spine (Phila Pa 1976). 2002 May 1;27(9):911-7
11979160
Spine (Phila Pa 1976). 2003 Apr 15;28(8):750-3; discussion 753-4
12698115