Trauma patients (TP) often develop an imbalanced immune response, frequently leading to infectious post-injury complications. Monocytes, part of innate immune system, show diminished HLA-DR-expression and impaired pro-inflammatory cytokine-release upon stimulation after trauma. Monocytes recognize lipopolysaccharide (LPS) via TLR4 and CD14. Data on TLR4-expression in TP's monocytes ... [Show full abstract] are conflicting. Moreover, there are no studies describing TLR4-expression after secondary stimulation or TLR4- and HLA-DR-co-expression after trauma.
20 TP [ISS≥16] and ten healthy volunteers (HV) were included. Ex vivo in vitro LPS-stimulation (10 μg/mL, 24 h) of whole blood was performed daily until day 10. IL-1β-release was determined by ELISA. TLR4-expression on HLA-DR-positive and -negative monocytes prior and after their stimulation with the leukocyte-activation-cocktail (LAC) was determined by flow cytometry.
LPS-induced IL-1β-release was significantly diminished in TP showing a recovery after day 5 compared to HV (p < 0.05). TLR4-expression in unstimulated samples from TP was significantly reduced at ED compared to HV. LAC-stimulated monocytes from TP had continuously reduced TLR4-expression compared to HV during the whole time course. HLA-DR-expression was lowered after trauma, and even more profound after stimulation. Co-expression analysis indicated that HLA-DR- monocytes may be responsible for impaired TLR4-expression after stimulation in TP. Ratio of CD14+ monocytes to leukocytes was significantly increased in the later post-injury phase.
Next to reduced monocyte function, TP show diminished TLR4-expression after stimulation. Here, a possible mechanism for endotoxin tolerance in monocytes after major trauma is shown. Additionally, impaired TLR4-expression on naive HLA-DR- monocytes may contribute to functional suppression of monocytes after trauma.