Ma Y, Li R, Wang J, et al. - Usually, changes in varieties of inflammation proteins accompany bloodstream infection (BSI). In the previous study, the infection arms showed a high expression of inter-α-trypsin inhibitor heavy chain H4 (ITIH4) relative to the normal control arm. Researchers here used Escherichia coli infected mice model and clinical serum samples to validate the concentration of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), as well as ITIH4, in ELISA method. They used cytokines (IL-6, TNF-α, IL-10 and lipopolysaccharide (LPS)) to stimulate the HepG2 cell model to determine the cytokines influencing the expression of ITIH4. Prior to IL-6 and LPS stimulation, JAK/STAT inhibitor was treated. In mice model, the infection arms showed an increase in IL-6, TNF-α, as well as IL-10, relative to the normal control arm. Increase in ITIH4 was noted in serum and liver tissue of mice model from 1 h to 128 h, which was remarkably different from that of the normal control arm. Besides, there was a great increase in ITIH4 in the bacterial infection arm relative to the fungemia arm, mycoplasma pneumoniae (MP) arm and febrile arm in clinical serum samples. Overall findings suggest ITIH4 to be a new biomarker in diagnosing the bacterial bloodstream infection. Elevation in ITIH4 occurs in the bacteremia mainly due to regulation by IL-6 or LPS through JAK/STAT pathway. They identified a good performance of ITIH4 in differentiating the bacteremia from fungemia or MP infection.