Ocean State Clinical Coordinating Center
Publications
Opal SM, Artenstein A, Cristofaro PA, Jhung J, Palarady JE, Parejo NA, Lim Y-P. Inter-alpha Inhibitor proteins are endogenous furin inhibitors and are protective in experimental anthrax intoxication. Infection and Immunity 2005;73(8):5101-5105.
Abstract
Inter-alpha-inhibitor protein (IIp) functions as an endogenous serine protease inhibitor in human plasma, and IIp levels diminish rapidly during acute inflammatory states. One potential target for IIp is furin, a cell-associated serine endopeptidase essential for the activation of protective antigen and the formation of anthrax lethal toxin (LT). IIp blocks furin activity in vitro and provides significant protection against cytotoxicity for murine peritoneal macrophages exposed to up to 500 ng/ml LT. A monoclonal antibody (MAb), 69.31, that specifically blocks the enzymatic activity of IIp eliminates its protective effect against LT-induced cytotoxicity. IIp (30 mg/kg of body weight) administered to BALB/c mice 1 hour prior to an intravenous LT challenge resulted in 71% survival after 7 days compared with no survivors among the control animals (P < 0.001). We conclude that human IIp may be an effective preventative or therapeutic agent against anthrax intoxication.
Objective: To define and introduce the PIRO model for categorizing sepsis in infants and children.
Design: A summary of the literature published during the 5 yrs since this concept has been formulated, along with a consensus opinion of experts in the field of sepsis and septic shock.
Results: The imprecision and intrinsic heterogeneity of the patient population defined as septic has prompted the introduction of a new sepsis classification system known as PIRO. PIRO stands for predisposition, infection, response, and organ dysfunction. It is hoped that by defining the septic process through a detailed analysis of each of its component parts, the development of sepsis will be better understood. This may contribute to improved therapeutic interventions for sepsis in the future.
Conclusions: The PIRO model is a conceptual framework for understanding sepsis that has many favorable attributes. The PIRO model should be directly tested in both the research laboratory and in clinical trial designs to determine the practical value and clinical relevance of this new classification scheme for sepsis.
Back | Steven Opal, MD |
