Induction of type 2 and 3 deiodinase in the blood cells of critically ill patients.

Altered type 2 and 3 deiodinase (D2 and D3) can disrupt thyroid hormone metabolism and contribute to non-thyroidal illness syndrome (NTIS). The impact of the colocalization of D2 and D3, and their expression in immune cells isolated from critically ill patients, are still not fully understood. Our objective was to assess the D2 and D3 in the neutrophils and monocytes of patients admitted to the intensive care unit (ICU) for any cause. Blood samples were collected from 96 ICU patients at admission and on day 7. We employed different cell gradients and flow cytometry to separate and purify cells from whole blood. Parameters indicating redox balance were measured, including total carbonyls, sulfhydryl content and glutathione (GSH) levels. The expression and colocalization of DIO2 and DIO3 were evaluated through RNAscope, real-time PCR (polymerase chain reaction) and immunofluorescence. The formation of carbonyls, a marker for oxidative damage to proteins, was elevated in all patients, while sulfhydryl and GSH levels were found to be reduced. The expression of DIO2 and DIO3 in neutrophils and monocytes from both surviving and deceased patients demonstrated significant variations in localization. Notably, elevated levels of D3 protein showed distinct distribution patterns between the groups. Levels of T3 in each cell type varied and were correlated with patient outcomes. The specific distribution of these enzymes has also been associated with prognosis. The set of these findings enhances our understanding of the pathophysiology of NTIS and may provide valuable information for prognostic assessments.