Serum Caspase-1 as an Independent Prognostic Factor in Traumatic Brain Injured Patients

Abstract

Background: The objectives of this study were to assess the association between serum caspase 1 levels and known clinical and radiological prognostic factors and determine whether caspase 1was a more powerful predictor of outcome after traumatic brain injury (TBI) than clinical indices alone, to determine the association between the serum levels of caspase 1 and the 6-month outcome, and to evaluate if there is any association between caspase 1 with clinical and radiological variables.

Methods: This prospective and observational study was conducted in a university hospital and included patients with TBI who required hospital admission. Serum samples were collected at hospital admission and 24 h after TBI. Caspase 1 levels were determined by enzyme-linked immunosorbent assay. Receiver operating characteristic curves were obtained to test the potential of caspase 1 to predict mortality (Glasgow Outcome Scale Extended score of 1) and unfavorable outcome (Glasgow Outcome Scale Extended scores of 1-4). Multivariate logistic regression was used to assess the effect of serum caspase 1 levels, adjusted by known clinical and radiological prognostic indices, on the outcome.

Results: One hundred thirty-two patients and 33 healthy controls were included. We obtained 6-month outcome in 118 patients. On admission, the mean serum levels of caspase 1 were higher in patients with TBI compared with controls (157.9 vs. 108.5 pg/mL; p < 0.05) but not at 24 h after TBI. Serum caspase 1 levels on admission were higher in patients with unfavorable outcomes (189.5 vs. 144.1 pg/mL; p = 0.009). Similarly, serum caspase 1 levels on admission were higher in patients who died vs. patients who survived (213.6 vs. 146.8 pg/mL; p = 0.03). A logistic regression model showed that the serum caspase 1 level on admission was an independent predictor of 6-month unfavorable outcomes (odds ratio 1.05; 95% confidence interval 1-1.11; p = 0.05). Caspase 1 levels were higher in patients with severe TBI compared with those with moderate TBI, those with mild TBI, and healthy controls (p < 0.001). We did not find any correlation between caspase 1 and the radiological variables studied.

Conclusions: In this cohort of patients with TBI, we show that serum caspase 1 protein levels on admission are an independent prognostic factor after TBI. Serum caspase 1 levels on admission are higher in patients who will present unfavorable outcomes 6 months after TBI. Caspase 1 levels on admission are associated with the injury severity determined by the Glasgow Coma Scale.

Keywords: Caspase 1; Inflammasome; Inflammation; Innate immunity; Traumatic brain injury.