Cytokine response to critical illness and its relation to amino acid metabolism

Critical illness is characterized by an intense inflammatory response that triggers major metabolic changes with protein catabolism resulting in major losses of muscle mass. The intensity of the inflammatory response appears as the principal driver of the changes involved in outcome, and especially those affecting protein metabolism and muscle catabolism, and resistance to nutrition. The present exploratory study aims to clarify the role of the different cytokines in amino acid metabolism.

In this post-hoc analysis of the previously published observational study, including 51 critically ill patients and 49 healthy controls aiming at identifying patient changes in amino acid metabolism, we assessed the association between a panel of cytokines and blood levels of amino acids (AA) and their turnover. The subjects were matched for age, sex, and BMI. The study was conducted in postabsorptive state. Blood analysis included cytokines (determined by Luminex), C-reactive protein (CRP or hsCRP), and AA.

8 mL solution containing 18 stable AA tracers administered as a pulse to calculate amino acid whole body production (WBP). WBP was calculated from fitted decay curves. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using Generalized Linear Model (GLM) t and stepwise regression. Data as means [95%CI].

The study included 51 critically ill patients (age 63 yrs [58, 68], APACHEII 21.6 [20, 24]) and 49 matched healthy controls (age 57 yrs [52, 61]). While anthropometric characteristics were similar between critically ill patients and healthy adults, phase angle was lower (3.9 [3.5, 4.2] vs 6.0 [5.6, 6.3], p < 0.001), most AA blood levels were lower, while most cytokine levels were significantly higher. IL-6 and CRP were strongly associated (p < 0.001). IL-6 was the cytokine with the strongest association with the AA blood levels and WBP alterations in patients. Three patterns of changes in the plasma cytokine concentrations were observed. Of the 37 cytokines measured, 12 were higher in ICU patients, 5 were lower, and the rest were similar.

The present study shows a comprehensive picture of inflammation and simultaneous alterations of AA metabolism. The levels of IL-6 and CRP may become a good indicator of the metabolic capacity to respond positively to nutrition therapy.

Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).