Research article

Imbalance of tissue inhibitors of metalloproteinases (TIMP) – 1 and – 4 serum levels, in patients with inflammatory bowel disease

Andreas N Kapsoritakis¹ , Anastasia I Kapsoritaki² , Ioanna P Davidi¹ , Vasilios D Lotis¹ , Anastasios C Manolakis¹ , Petros I Mylonis¹ , Aikaterini T Theodoridou² , Anastasios E Germenis² and Spyros P Potamianos¹

¹  Department of Gastroenterology, University of Thessaly, School of Medicine, Larissa, Greece

²  Department of Immunology and Histocompatibility, University of Thessaly, School of Medicine, Larissa, Greece

author email corresponding author email

BMC Gastroenterology 2008, 8:55doi:10.1186/1471-230X-8-55

Published:	26 November 2008

Abstract

Background

Tissue inhibitors of metalloproteinases (TIMPs) play a key role in tissue degradation and remodeling. Since chronic inflammation is associated with tissue remodeling in inflammatory bowel disease (IBD), we evaluated serum TIMP-1 and TIMP-4 levels in IBD patients, in comparison with healthy controls (HC).

Methods

TIMP-1, TIMP-2 and TIMP-4 serum levels were determined in 53 patients with ulcerative colitis (UC), 52 patients with Crohn's disease (CD) and 50 HC, by means of commercially available enzyme-linked immunosorbent assays. The levels of TIMPs were evaluated with regard to the levels of inflammatory markers, such as C reactive protein (CRP) and serum amyloid A (SAA) and the clinical characteristics of patients, so that potential correlations could be recorded.

Results

Mean serum TIMP-1 levels were 414.9 ± 17.6 ng/mL in UC patients, 446.1 ± 22.8 ng/mL in CD patients and 296.5 ± 20.6 ng/mL in HC. UC and CD patients had significantly higher serum TIMP-1 levels when compared to HC, (p < 0.0001 in both groups). Mean serum TIMP-1 levels were significantly higher in patients with active IBD (450.5 ng/mL) in comparison with patients with inactive disease (417.3 ng/mL, p = 0.03). Moreover, males showed significantly higher mean serum TIMP-1 levels (399.8 ng/mL), compared to females (368.5 ng/mL, p = 0.04). Mean serum TIMP-2 levels did not differ between UC and CD patients or HC (p > 0.05 in all cases). Mean serum TIMP-4 levels were 1761.2 ± 67.7 pg/mL in UC patients, 1708.1 ± 73.4 pg/mL in CD patients and 5573.4 ± 1246.3 pg/mL in HC. UC and CD patients had significantly lower serum TIMP-4 levels when compared to HC (p = 0.008 and p = 0.02 respectively). Mean serum TIMP-4 levels were significantly lower in males (2772.9 pg/mL), compared to females (3299.0 pg/mL, p = 0.01). In addition, CRP levels showed a statistically significant correlation with TIMP-1 (r = 0.247, p = 0.01), and TIMP-4 levels (r = 0.217, p = 0.03). Similarly, there was a statistically significant correlation between SAA levels and both TIMP-1 (r = 0.264, p = 0.008) and TIMP-4 serum levels (r = 0.212, p = 0.03).

Conclusion

An imbalance between TIMP-1 and TIMP-4 serum levels is present in IBD patients. TIMP-1 levels could be used not only for diagnostic purposes but also for the assessment of activity in IBD. Gender tends to influence TIMP-1 and TIMP-4 serum levels. These new findings bring into question the potential role of TIMPs in IBD, thus underlining the need for future studies which could offer new insight into this matter.