Cytokine levels (IL-4, IL-6, IL-8 and TGFß) as potential biomarkers of systemic inflammatory response in trauma patients.

PURPOSE: Much research is now being conducted in order to understand the role of cytokines in the development of the inflammatory response following trauma. The purpose of this study was to evaluate whether serum levels of certain cytokines, measured immediately after initial injury, can be used as potential biomarkers for predicting the development and the degree of severity of the systemic inflammatory response (SIRS) in patients with moderate and severe trauma. METHODS: We conducted a prospective study with 71 individuals of whom 13 (18.3 %) were healthy controls and 58 (81.7 %) were traumatized orthopaedic patients who were categorized into two groups: 31 (43.6 %) with moderate injuries and 27 (38.1 %) patients with severe orthopaedic trauma. Thirty cc of heparinized blood were drawn from each individual within a few hours after the injury. Serum levels of pro-inflammatory, regulatory and anti-inflammatory cytokines were measured in each individual participant. RESULTS: High levels of pro-inflammatory cytokines IL-1ß,-6,-8,-12, tumour necrosis factor alpha and interferon gamma were found in all injured patients compared to healthy controls. Only IL-6 and IL-8 were significantly higher in the injured patients. Levels of the regulatory cytokines, transformed growth factor beta (TGF-ß) and IL-10 were higher in the injured patients, but significant only for TGF-ß. Levels of IL-4 were significantly lower in the injured groups as compared to the controls. CONCLUSIONS: Secretion of large amounts of pro-inflammatory cytokines and decreased level of anti-inflammatory cytokines during the acute phase of trauma may lead to the development of systemic inflammatory response syndrome (SIRS) in unstable polytraumatized patients. SIRS may result in life threatening conditions as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). High levels of IL-6, IL-8, TGFß and low levels of IL-4 were found to be reliable markers for the existence of immune reactivity in trauma patients. More research is needed to study pattern of cytokine levels along the acute period of injury, after surgical interventions and during recovery.

Possible association of Toll-like receptor 9 polymorphisms with cytokine levels and posttraumatic symptoms in individuals with various types of orthopaedic trauma: early findings.

BACKGROUND: Although TLR9 polymorphisms may be associated with cytokine dysregulation, its role in regulation of cytokines due to bodily trauma or in relation to acute stress symptoms or posttraumatic stress symptoms (ASS/PTS) has not been evaluated. AIMS: To assess serum cytokine levels and levels of ASS and PTS in relation to four common TLR9 single-nucleotide polymorphisms (SNPs) in individuals with various types of orthopaedic trauma. METHODS: Forty-eight accident-injured individuals, aged 20-60 years were studied. Serum cytokine levels and TLR9 SNPS (1486T/C, 1237T/C, 1174G/A and 2848G/A) were assessed together with intensity of ASS and PTS symptoms. RESULTS: Statistically significant higher serum levels of IL-12 and IL-1ß (p<.05) were found in individuals heterozygous for TLR9-1237 (TC) than in individuals expressing the most common TLR9-1237 type (TT), while differences in levels of IL-6 were not significant. Also, marginally significant levels of IL-6 were found in individuals expressing the common TLR9-1174 (GG) compared with individuals homozygous (AA) or heterozygous (GA) for this SNP. They also had non-significant higher intensity of ASS symptoms. A trend of higher PTS levels in individuals expressing the most common type TLR9-1174 (GG) was found, contrary to homozygous (AA) and heterozygous individuals (GA). CONCLUSIONS: The results of this pilot study suggest that accident-injured individuals with certain TLR9 polymorphisms express higher levels of pro-inflammatory cytokines (IL-1ß, IL-6 and IL-12). The associations of TLR9 SNPSs with increased risk of ASS or PTS should be further studied in larger groups of such patients.

Cytokine levels as potential biomarkers for predicting the development of posttraumatic stress symptoms in casualties of accidents.

BACKGROUND: Traumatic injuries are usually associated with increased secretion of pro-inflammatory cytokines, and are sometimes followed by the development of acute stress symptoms (ASS) and posttraumatic stress symptoms (PTSS). AIMS: To measure serum pro- and anti-inflammatory cytokines in accident casualties and to associate it with ASS at hospitalization, and with PTSS 1 month later. METHODS: Participants were 48 patients, aged 20-60, hospitalized following various orthopedic injuries including bone fractures, and 13 healthy volunteers matched for gender. At hospitalization (Time 1), 30 ml heparinized venous blood were drawn and cytokines levels in serum were assessed; participants filled out the Acute Stress Disorder Inventory (ASDI), COPE, and injury-related questionnaires. One month later (Time 2), 26 participants filled out the Posttraumatic Disorder Symptom Scale (PDS). RESULTS: High serum levels of IL-6, IL-8, and TGF-beta and low levels of serum IL-4 and IL-10 were found in injured patients as compared with controls, When controlling for age and severity of injury in the regression analysis, higher levels of IL-6 and IL-8 and lower TGF-beta were predicted by higher ASS and higher use of and emotion-focused coping. Higher PTSS scores at Time 2 were predicted by higher levels of IL-8, lower levels of TGF-beta, and higher ASS measured at Time 1. CONCLUSIONS: High levels of the pro-inflammatory cytokine IL-6 and IL-8 and lower levels of the regulatory cytokine TGF-beta should be further assessed as a possible risk factor or a bio-marker of PTSS in accident casualties.