Procalcitonin augments mortality in experimental sepsis
Clinical Infectious Diseases
Intro: We reported that the high levels of serum procalcitonin (ProCT) seen in sepsis correlate with the severity of sepsis and are predictive of outcome. We also reported that ProCT immune-neutralization improves survival in sepsis. Thus, we sought to evaluate its potential toxicity by giving ProCT to septic hamsters. Methods: Sepsis was induced in Golden-Syrian hamsters using intra-abdominal implants of agar pellets impregnated with 5 × 108 cfu of Esherichia coli. At the time of initial septic challenge, each hamster was given either 3 μg of extracted human ProCT (experimental group) or an equivalent volume of hamster serum (control group) by IV injection. The animals were observed for 72 hours with mortality as the primary endpoint. In a parallel experiment, hamsters were sacrificed at 2 and 12 hours post septic challenge to measure serum cytokines and chemistry. Results: In septic control animals (n=16), there was 50% mortality at 48 hours and 56% mortality at 72 hours. In the experimental group (n=16) receiving ProCT, mortality was 87% at 48 hours (p=0.03) and 94% at 72 hours (p=0.02). We found significant hypocalcemia and hyperphosphatemia at 12 hours in the septic control hamsters. ProCT injections did not alter these changes. TNFα rose progressively in septic controls (7.02 ng/ml at 2 hr and 10.9 ng/ml at 12 hr.). This response was blocked by ProCT administration (5.05 ng/ml at 2 hr and 5.09 ng/ml at 12 hr). Conclusions: ProCT significantly increased mortality in the septic animals. Injected ProCT did not alter the low calcium or high phosphate levels seen in septic controls; however, it did block the TNFα response. The effects of ProCT that make it lethal in sepsis require additional research to develop effective therapy.
Whang, K., White, J., Snider, R., Nylen, E., Li, Q., Tamarkin, L., & Becker, K. (1997). Procalcitonin augments mortality in experimental sepsis. Clinical Infectious Diseases, 25 (2). Retrieved from https://hsrc.himmelfarb.gwu.edu/smhs_medicine_facpubs/4984