Toll-like receptor responses are suppressed in trauma ICU patients

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• 作者：Travis L. Holloway ; MD^a ; Susannah E. Nicholson ; MD^a ; Meenakshi Rani ; PhD^a ; Andrew P. Cap ; MD ; PhD^a ; ^b ; Martin G. Schwacha ; PhD^a ; ^b ; ^{schwacha@uthscsa.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cytokines ; Inflammation ; Whole blood ; PAMPs ; DAMPS
• 刊名：Journal of Surgical Research
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：206
• 期：1
• 页码：139-145
• 全文大小：376 K

文摘

Inflammation and activation of the innate immune system are often associated with traumatic injury and may involve alterations in toll-like receptor (TLR)-mediated responses.

Methods

A prospective observational study was designed and conducted. Twenty-one severely injured (ISS = 16-41) trauma intensive care unit (ICU) patients and six healthy volunteers that served as controls were enrolled. Anticoagulated whole blood was collected at 2-12 d after ICU admission and incubated in the presence of media alone (baseline), zymosan (TLR2 agonist) or lipopolysaccharide (LPS; TLR4 agonist) for 3 h. Supernatant levels of inflammatory cytokines (IL-1β, IL-6, IL-10, and TNFα) were determined.

Results

TLR2-mediated and TLR4-mediated activation of whole blood cell cultures from both healthy volunteers and subjects-induced elevated cytokine levels over that observed in unstimulated cultures. Baseline values of IL-6 were significantly elevated in subject cultures as compared to healthy volunteers. Healthy volunteer cultures had 2-3-fold greater levels of IL-6 and TNFα than subject cultures when stimulated with zymosan (TLR2 agonist) or LPS (TLR4 agonist). IL-1β and IL-10 levels did not differ significantly between healthy volunteers and subjects.

Conclusions

The ability of circulating leukocytes from trauma ICU patients to be activated by TLR agonists is markedly suppressed and may play a role in the development of subsequent infectious complications.