Reply to Re: Hepatocyte Growth Factor and Inflammatory Bowel Disease

Abstract

To the Editors: We would like to thank Dr. Couper for reading and commenting on our paper. The assay we used is an ELISA manufactured by an American company (R and D systems), which has been tested for specificity to HGF. We have technical information on the assay I will mail to Dr. Couper upon request, or he should feel free to contact the company directly. Dr. Couper states that the HGF levels seen in our IBD population are similar to “control” levels in his institution's assay. In our study using our assay, the levels are clearly and statistically different from controls. This most probably reflects differences in the assays themselves, and emphasizes the need to use a single assay for both cases and controls when doing studies such as this one. Dr. Couper also notes that in his experience, the elevation of serum HGF we report is a small one. He asks whether these serum levels are “clinically significant,” and whether the elevated serum HGF we have seen is simply an epiphenomenon of inflammation. The elevated HGF level we report is statistically significant, and quantitatively comparable to elevations of other serum cytokines (interleukin-6, tumor necrosis alpha) that have been published previously by other investigators. To use an analogy with tumor necrosis factor (TNF), initial studies in IBD showed only modest elevations of serum TNF. However, the efficacy of infliximab as a therapy makes it clear that TNF is a clinically significant mediator of inflammation in Crohn disease. If the serum elevations of HGF in IBD are caused by release of cytokines into the blood from an inflamed gut, the small elevations seen in serum may reflect much higher elevations in intestinal mucosa. Hepatocyte growth factor release is unlikely to be an early event in the cascade of intestinal inflammation seen in IBD patients. However, HGF has biologic effects (increased angiogenesis, altered vascular permeability, facilitation of wound healing) which suggest this cytokine may play a role in the pathophysiology of IBD. Some medications used in the treatment of IBD (e.g., 6-mercaptopurine) have antiangiogenic properties, and inhibition of angiogenesis may be a mechanism of their efficacy. We hope our study will stimulate further studies of this and other angiogenesis factors in IBD, at both the serum and mucosal level. Athos Bousvaros, MD Maya Srivastava, MD