Studies on Heparin Binding protein in bacterial infections

Sammanfattning: Infectious diseases remain a major health problem, where sepsis and other severe bacterial infections are common causes of morbidity and mortality, and are associated with high costs for the community. The importance of early and appropriate treatment of sepsis and severe bacterial infections has been underlined by many and since sepsis is more prevalent and has a higher mortality rate than for instance acute myocardial infarction, there is a need for improvement. The heparin-binding protein (HBP, azurocidin, CAP37) is a multifunctional neutrophil-derived protein. HBP has been shown to be a powerful inducer of vascular leakage. In this thesis we demonstrate that HBP could have a potential role as a new biomarker for severe infections. First, the levels of HBP in plasma were closely correlated to development of circulatory failure in sepsis. This could help improving early identification of patients in the emergency department in need of aggressive treatment. Furthermore, we found that serial HBP measurements in plasma might be useful in predicting outcome in critically ill intensive care unit patients. We also found HBP to be present in higher amount in the cerebrospinal fluid of patients with acute bacterial meningitis compared to non-bacterial meningitis. Finally, we demonstrated that activation of the contact-system and release of HBP is present in the inflamed skin in erysipelas, suggesting a pathophysiological role in this relatively prevalent condition. In conclusion, this thesis provides some novel findings stressing the important role of HBP in severe infections, its potential usefulness as a new biomarker, and maybe a future target of treatment.