Exploring the immune status of sepsis patients through Tim-3 expressed on monocytes and IL-12

Purpose: Sepsis is a severe infection disease that leads to immune dysfunction. The expression of T cell Ig and mucin domain protein-3(Tim-3) on monocytes has been suggested to be an important immune regulator during infection as it was shown to regulate the production of IL-12 both in vitro and in vivo. The expression of Tim-3 on monocytes and its relationship to IL-12 expression in sepsis patients remain unclear. Methods: Our study included 36 patients with differing severities of sepsis (12 patients with sepsis, 16 patients with severe sepsis, 8 patients with septic shock) and 11 normal controls. The expression of Tim-3 on monocytes was evaluated by flow cytometry. IL-12 mRNA in peripheralbloodcells was assayed using real-time PCR (RT-PCR). Results: The expression of Tim-3 on monocytes and IL-12 mRNA were significantly elevated in sepsis and severe sepsis patients in comparison with normal controls. However, Tim-3 and IL-12 levels were significantly decreased in patients with septic shock compared to patients with severe sepsis. The relevant risk factors for death and Tim-3 were evaluated using logistic regression analysis; the odds ratio (OR) for Tim-3 was 1.218 (p<0.05). We found that Tim-3 expression on monocytes was positively correlated with IL-12 expression (Spearman correlation coefficient=0.782, p<0.001). Conclusion: Our findings indicate that Tim-3 is involved in regulating the function of monocytes in sepsis patients and that low expression of Tim-3 is associated with the immune suppression of monocytes during the early stage of septic shock. Tim-3 may potentially act as an indicator for the prognosis of septic shock and guide future developments of immunotherapy approaches.