Dynamic changes of matrix metalloproteinases and their tissue inhibitors in severe sepsis

Abstract Purpose Little is known about the dynamic changes of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in sepsis. Our aim was therefore to investigate the time course of MMPs and their inhibitors in patients experiencing severe sepsis. Methods Our prospective controlled analysis included 38 patients with severe sepsis. Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured daily at a 5-day-long period with enzyme-linked immunosorbent assay. Seventeen healthy volunteers were invited as controls. Results MMP-2 showed no difference compared to controls, whereas significantly elevated MMP-9 levels were detected on admission ( P < .005). Significantly elevated but declining TIMP-1 levels were measured during the whole trial ( P < .002-.004). Except for the second day, TIMP-2 levels were significantly lower than controls ( P < .05-.009). MMP2/TIMP-1 ratios were significantly lower in septic patients ( P < .03-.006), whereas MMP-2/TIMP-2 ratios were elevated throughout our study ( P < .03-.006). MMP-9/TIMP-1 ratios were significantly lower at the first 3 days ( P < .05-.008). MMP-9/TIMP-2 was significantly elevated on admission ( P < .006). Conclusions Our research is the first follow-up study dealing with MMPs, TIMPs, and their ratios in severe sepsis. Our results indicate that MMPs and TIMPs may play a crucial role in severe sepsis, especially TIMP-1, MMP-9, and possibly TIMP-2, after an extensive study.