Circulating protein carbonyls are specifically elevated in critically ill patients with pneumonia relative to other sources of sepsis.

ABSTRACT

BACKGROUND: Septic shock is a life-threatening dysregulated response to severe infection and is associated with elevated oxidative stress. We aimed to assess protein carbonyls in critically ill patients with different sources of sepsis and determine the effect of vitamin C intervention on protein carbonyl concentrations. METHODS: Critically ill patients with septic shock (n = 40) were recruited, and sources of sepsis and ICU severity scores were recorded. The patients were randomised to receive either intravenous vitamin C (100 mg/kg body weight/day) or placebo infusions. Blood samples were collected at baseline and daily for up to three days for measurement of cell counts, vitamin C concentrations, protein carbonyls, C-reactive protein, and myeloperoxidase concentrations. RESULTS: Protein carbonyl concentrations increased 2.2-fold in the cohort over the duration of the study (from 169 to 369 pmol/mg protein; p = 0.03). There were significant correlations between protein carbonyl concentrations and ICU severity scores (APACHE III r = 0.47 and SOFA r = 0.37; p < 0.05) at baseline. At study admission, the patients with pneumonia had nearly 3-fold higher protein carbonyl concentrations relative to the patients with other sources of sepsis (435 vs 157 pmol/mg protein, p < 0.0001). The septic patients had deficient vitamin C status at baseline (9.8 ± 1.4 µmol/L). This increased to 456 ± 90 µmol/L following three days of intravenous vitamin C intervention. Vitamin C intervention did not attenuate the increase in protein carbonyl concentrations. CONCLUSIONS: Circulating protein carbonyls are specifically elevated in critically ill patients with pneumonia relative to other sources of sepsis. The reasons for this are currently unclear and may indicate a mechanism unique to pulmonary sources of sepsis. Intravenous vitamin C administration did not attenuate the increase in protein carbonyls over time.