Interferon-γ (IFNγ), a double-edge sword that affects prognoses in critically ill patients: A prospective study

Abnormal inflammatory responses and viral infections play a critical role in the pathogenesis of critical illnesses. Critically ill patients frequently develop multiple organ dysfunction syndrome (MODS), a key determinant of clinical outcomes and a marker of poor prognosis. Interferon-γ (IFNγ), an important inflammatory regulatory cytokine, may serve as a more accurate indicator of viral infection severity and holds potential as a predictor of MODS and prognosis in critically ill patients.

To evaluate the association between IFNγ levels and clinical outcomes in critically ill patients.

This prospective study, conducted from January 1 to May 31, 2023, at Peking Union Medical College Hospital, used data from electronic medical records to collect baseline characteristics, ICU parameters, laboratory tests, and clinical outcomes. MODS was diagnosed on the basis of Sequential Organ Failure Assessment (SOFA) scores. Generalized Additive Models were employed to explore linear and nonlinear associations, while survival analyses were performed using the Kaplan-Meier method.

A total of 208 patients were analyzed. IFNγ levels demonstrated a significant positive linear correlation with MODS in both sepsis (odds ratio [OR] 1.041, 95% confidence interval [CI]: 0.962-1.126) and non-sepsis (OR 1.025, 95% CI: 0.907-1.157) subgroups (intergroup P < 0.001). The relationship between IFNγ levels and 28-day mortality followed a U-shaped curve, with a threshold of 5.3 ng/mL. In the sepsis subgroup, patients with low IFNγ levels exhibited poorer prognoses compared with those with high IFNγ levels (P = 0.021). No significant difference in prognosis was observed between procalcitonin (PCT) subgroups (P = 0.087). Among patients with elevated IFNγ levels, a positive correlation between PCT and 28-day mortality was identified (OR 1.098, 95% CI: 0.815-1.481).

IFNγ is strongly associated with MODS and prognosis in critically ill patients, highlighting its potential as a biomarker for predicting MODS occurrence and patient outcomes. These findings underscore the clinical value of IFNγ in critical care, providing a foundation for further research in this area.