The significance and role of the receptor and inflammatory factors in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by diffuse alveolar damage and severe hypoxemia, with mortality rates remaining high despite advances in supportive care. Cytokine dysregulation and genetic susceptibility are thought to play central roles in its pathogenesis, but data in Chinese populations remain limited. This study aimed to investigate the associations of circulating cytokine levels and genetic polymorphisms with ARDS risk. We enrolled 240 patients with ARDS and 420 age- and sex-matched healthy controls. Serum concentrations of TLR2, TLR4, TLR9, IL-1, IL-6, IL-8, IL-10, IL-17, TNF-α, and IFN-γ were quantified by ELISA. Selected single-nucleotide polymorphisms (SNPs) in TLR and cytokine genes were genotyped using PCR-RFLP with rigorous quality control, including Hardy-Weinberg equilibrium checks. Associations with ARDS risk were estimated using multivariable logistic regression adjusted for age, sex, BMI, smoking, diabetes, and hypertension. Multiplicity was addressed with the Benjamini-Hochberg false discovery rate (FDR). ARDS patients exhibited significantly elevated serum concentrations of TLR2, TLR4, TLR9, IL-1, IL-8, IL-10, IL-17, and TNF-α compared with controls (all p < 0.05), with IL-1 and TNF-α remaining significant after FDR correction. Several genetic variants were strongly associated with ARDS susceptibility, including TLR2 - 196 to - 174 del (OR = 1.85; 95% CI, 1.23-2.77), TLR9 rs352140 AA (OR = 2.97; 95% CI, 2.16-4.08), IL-1B + 3954 TT (OR = 5.01; 95% CI, 2.85-8.81), IL-10 - 1082 GA/AA, TNF-α - 308 AA, and IFN-γ + 874 TT. After FDR control, significant associations persisted for TLR2 - 196 to - 174 del, TLR9 rs352140, and IL-1B + 3954. Sensitivity analyses stratified by ARDS etiology (pneumonia, sepsis, trauma, other) yielded consistent results. Both inflammatory dysregulation and host genetic variation contribute to ARDS susceptibility in Chinese patients. Elevated cytokines (IL-1, TNF-α, IL-10) and specific polymorphisms (TLR2 - 196 to - 174 del, TLR9 rs352140, IL-1B + 3954) may serve as candidate biomarkers for risk stratification. These findings warrant validation in larger multicenter cohorts and exploration of their prognostic value in clinical practice.