Introduction: In a sizable proportion of Crohn's disease (CD) patients recurrent disease develops following intestinal resection. We have previously demonstrated, in patients, that active CD is associated with decreased plasma levels of intact Insulin-like Growth Factor Binding Protein 3 (IGFBP-3). IGFBP-3 via binding of Insulin-like Growth Factor, an important cell growth factor, and via an independent apoptosis inducing mechanism, inhibits cell growth. It is believed that the intact IGFBP-3 protein, rather than the degraded protein, has the independent cell growth inhibitory properties. Because the loss of this growth protein might associated with postoperative relapse in CD, we to studied the concentration of IGFBP-3 and its protease MMP-9 (matrix metalloproteinase 9) in CD patients undergoing open colectomy.
Methods: Plasma was collected before surgery and on postoperative days (POD) 1 and 3 from 11 CD patients undergoing open colectomy. The concentration of intact IGFBP-3 in the plasma was calculated using a method that included both ELISA and Western Blot assay. Plasma proteolytic activity was assessed by zymography. The level of MMP-9 was measured via ELISA. Statistical analysis was performed using Wilcoxon's test.
Results: The level of intact IGFBP-3 was significantly decreased on POD1, 1409±1220 ng/ml and on POD3, 1107±1186 ng/ml compared to preoperative levels, 2467±2885 ng/ml (p<0.05 for both comparisons). The predominant plasma protease, as revealed by protein size analysis in zymography, was MMP-9. The level of MMP-9 was significantly higher on POD3, 763.7±659.5 ng/ml compared to the pre-operative concentration, 449.5±422.3 ng/ml (p<0.05). Conclusion Surgical trauma leads to an increase the plasma concentration of MMP-9 serum and in the subsequent depletion of IGFBP-3. The duration of the IGFBP-3 decrease is unclear and the clinical significance, if any, of this alteration is also unknown. This potential mechanism for early recurrence in CD patients warrants further investigation.