Longitudinal change of serum inter-alpha-trypsin inhibitor heavy chain H4, and its correlation with inflammation, multiorgan injury, and death risk in sepsis

BackgroundInter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) inhibits infection-induced inflammation and multiorgan injury through several methods. The present study aimed to estimate the association of serum ITIH4 with inflammatory cytokines, multiorgan injury, and death risk in sepsis patients. MethodsSerum samples were collected to detect ITIH4 by enzyme-linked immunosorbent assay in 127 sepsis patients at admission (baseline), day (D)1, D3, and D7 after admission, as well as in 30 healthy controls (HCs). Additionally, 28-day mortality was recorded in sepsis patients. ResultsITIH4 was reduced in sepsis patients versus HCs (median [interquartile range]: 147.9 [78.2-208.8] vs. 318.8 [237.2-511.4] ng/ml) (p < 0.001). In sepsis patients, ITIH4 was associated with the absence of cardiovascular and cerebrovascular disease history (p = 0.021). Additionally, ITIH4 was negatively correlated with tumor necrosis factor-alpha (p < 0.001), interleukin (IL)-1 beta (p < 0.001), IL-6 (p = 0.019), IL-17A (p = 0.002), and C-reactive protein (p = 0.001), but positively related to IL-10 (p = 0.007). Moreover, ITIH4 was also inversely associated with Acute Physiology and Chronic Health Evaluation II score (p = 0.002), Sequential Organ Failure Assessment (SOFA) score (p < 0.001), SOFA-respiratory system score (p = 0.023), and SOFA-renal system score (p = 0.007). Interestingly, ITIH4 gradually increased from baseline to D7 (p < 0.001); besides, ITIH4 at baseline (p = 0.009), D1 (p = 0.002), D3 (p < 0.001), and D7 (p = 0.015) were all decreased in sepsis deaths versus sepsis survivors. ConclusionSerum ITIH4 is raised from baseline to D7 after disease onset, and it reflects the reduction of systemic inflammation, disease severity, and 28-day mortality for sepsis. However, further verification is required.

Automated summary

Serum ITIH4 is reduced in sepsis patients and correlated with inflammatory cytokines and disease severity. It gradually increases from disease onset to day 7 and reflects the reduction of systemic inflammation and 28-day mortality for sepsis.