Immunoneutralization of procalcitonin as therapy of sepsis.
Prior studies have demonstrated that the prohormone, procalcitonin (ProCT), and its component calcitonin precursors (CTpr) are increased in the serum of septic patients, correlate with the severity of the illness, and persist for relatively long periods of time. Animal studies in septic hamsters have revealed that the administration of ProCT is toxic and that immunoneutralization with IgG that is reactive to this molecule significantly improves survival. A large animal model of a very rapidly lethal polymicrobial sepsis has been developed in the pig in order to measure continuous physiological and metabolic parameters and also to compare the effects in this animal of an immunoneutralization, which is performed late in the course of the disease, to an identical, but early, therapy. Based upon the physiological and metabolic parameters, the late therapy, which was initiated during the fourth hour at a time when pigs were nearly moribund, was found to be as beneficial as early therapy. In both late and early therapy, the only animals to survive at the predetermined time of euthanasia were those which had received immunoneutralization therapy.
Becker
K L
KL
George Washington University and Veterans Administration Medical Center, 50 Irving Street NW, Washington, DC 20422, USA. klb1@erols.com
Nylén
E S
ES
Snider
R H
RH
Müller
B
B
White
J C
JC
D000818:Animals; D002116:Calcitonin / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D006224:Cricetinae; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000276:immunology*; D008647:Mesocricetus; D011498:Protein Precursors / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D018805:Sepsis / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D013997:Time Factors
D007074:Immunoglobulin G; D011498:Protein Precursors; D002116:Calcitonin