Travis L Holloway1, Susannah E Nicholson1, Meenakshi Rani1, Andrew P Cap2, Martin G Schwacha3. 1. Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas. 2. Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas; Blood Research, US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas. 3. Department of Surgery, The University of Texas Health Science Center at San Antonio, Texas; Blood Research, US Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas. Electronic address: schwacha@uthscsa.edu.
Abstract
BACKGROUND: 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.
BACKGROUND: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 ICUpatients to be activated by TLR agonists is markedly suppressed and may play a role in the development of subsequent infectious complications.
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