Interleukin-6 is a key factor for immunoglobulin-like transcript-4-mediated immune injury in sepsis

BACKGROUND: ILT4(+) monocytes seem to be associated with poor prognosis of sepsis in humans, but the exact mechanisms are unknown. This study aimed to examine the biological behaviors and effects of immunoglobulin-like transcript-4 (ILT4) levels on monocytes during sepsis and on the prognosis of sepsis. METHODS: ILT4(+/+) (WT) and ILT4-knockout (ILT4(−/−)) male BALB/c mice were used for sepsis modeling using cecal ligation puncture (CLP). Flow cytometry was used to measure the levels of ILT4 and major histocompatibility complex class II (MHC-II) on peripheral blood monocytes 24 h after CLP. ELISA was used to measure the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-12 at 0, 6, 12, and 24 h after CLP. Survival and prognosis were monitored over the course of 168 h. RESULTS: ILT4 was highly expressed in peripheral blood monocytes of septic mice 24 h after CLP (1292.00 ± 143.70 vs. 193.50 ± 52.54, p < 0.05). MHC-II levels on peripheral blood monocytes in ILT4(−/−) mice were significantly higher than those in WT mice (49.38 ± 5.66% vs. 24.25 ± 6.76%, p < 0.05). Serum IL-6 was significantly elevated 24 h after CLP (470.75 ± 88.03 vs. 54.25 ± 20.04, p < 0.05). The serum IL-6 levels were significantly lower in ILT4(−/−) mice compared with those in WT mice after CLP (241.25 ± 45.10 vs. 470.75 ± 88.03, p < 0.05), but TNF-α, IL-1β, and IL-12 were not changed. The survival of ILT4(−/−) mice was significantly better after CLP compared with that of WT mice. CONCLUSIONS: High levels of ILT4 on monocytes were observed in peripheral blood during sepsis and found to be associated with high serum IL-6 levels and low MHC-II levels on monocytes, possibly associated with higher mortality. ILT-4-IL-6-MHC-II could be a potential signaling pathway involved in sepsis.