C1-esterase inhibitor: An anti-inflammatory agent and its potential use inthe treatment of diseases other than hereditary angioedema

C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary an gioedema caused by a deficiency of C1-Inh. There is now accumulating eviden ce, obtained from studies in animals and observations in patients, that adm inistration of C1-Inh may have a beneficial effect as well in other clinica l conditions such as sepsis, cytokine-induced vascular leak syndrome, acute myocardial infarction, or other diseases. Activation of the complement sys tem, the contact activation system, and the coagulation system has been obs erved in these diseases. A typical feature of the contact and complement sy stem is that on activation they give rise to vasoactive peptides such as br adykinin or the anaphylatoxins, which in part explains the proinflammatory effects of either system. C1-Inh, belonging to the superfamily of serine pr oteinase inhibitors (serpins), is a major inhibitor of the classical comple ment pathway, the contact activation system, and the intrinsic pathway of c oagulation, respectively. It is, therefore, endowed with anti-inflammatory properties. However, inactivation of C1-Inh occurs locally in inflamed tiss ues by proteolytic enzymes (e.g., elastase) released from activated neutrop hils or bacteria thereby leading to increased local activation of the vario us host defense systems. Here we will give an overview on the biochemistry and biology of C1-Inh. We will discuss studies addressing therapeutic admin istration of C1-Inh in experimental and clinical conditions. Finally, we wi ll provide an explanation for the therapeutic benefit of C1-Inh in so many different diseases.