Discussion This is the first longitudinal study reporting the levels of MMP 2, MMP 8 and MMP 9 in the patients with severe sepsis. The main findings were the levels of MMP 2 and MMP 8 were up regulated in severe sepsis ARQ197 both in skin blister fluid and in the serum, MMP 2 levels were higher in skin blister fluid as well as in Inhibitors,Modulators,Libraries serum in more severe organ failures, and at three and six months the MMP levels had returned to normal. Similar to our results, increased MMP 8 levels have also been observed in a study with peritonitis patients, the majority of who had septic shock. MMP 8, also called the neutrophil collagenase, is predominantly released from neutrophilic granules upon infectious stimuli. However, in sepsis patients neutrophil infiltration to experimental skin blisters has shown to be attenuated by inflammatory media tors that down regulate chemotactic receptors on neutro phils.
Hence, the increased MMP 8 levels compared with controls Inhibitors,Modulators,Libraries seen in blister fluid possibly originate from circulating and marginated neutrophils, and translocates to the blister, or arise from other known cellular sources. Our studies did not reveal the source, but demonstrate, that in severe sepsis MMP 8 is up regulated even in healthy looking skin. Additively MMP 8 is not associated with organ failure parameters thus supporting the suggestion that MMP 8 has both pro and anti inflammatory roles. Surprisingly, Inhibitors,Modulators,Libraries in our data the 92 kDa proMMP 9 levels were suppressed in serum from the fourth day on and in the suc tion blister fluid from the first day.
Even when active and pro forms were calculated together the levels were sup pressed in sepsis in comparison with the control samples. Previously elevated MMP 9 levels have been reported within 24 hours from severe sepsis diagnosis. We collected the first samples within 48 hours from the beginning Inhibitors,Modulators,Libraries of the disease. The MMP 9 levels have been shown to peak early in lipopolysaccharide and Escherichia coli induced inflammatory response and return to normal within 24 hours. In the largest of previous patient samples MMP 9 was not significantly higher in sepsis patients and a negative correlation was found to organ fail ure parameters. This is in accordance with our results from the first study day. Our results on lower levels of MMP 9 from study day four are on another hand a novel finding.
Forms spliced to active MMP 9 could be found in a few patient samples but not in controls, implying that MMP 9 had been processed, Inhibitors,Modulators,Libraries whereas from day four onwards, the proMMP 9 levels dropped in a regulative fashion. Taken together, it seems that the MMP 9 levels are elevated at the very early phase of severe sepsis, but the levels drop later on. We found low MMP 9 levels also most in skin blister fluid sam ples of patients with severe sepsis in comparison with the controls.
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