Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock. METHODS: We genotyped two TREM-1 single nucleotide polymorphisms (SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis. RESULTS: TREM-1 rs2234246 A allele in the promoter region was significantly associated with the susceptibility of septic shock in recessive model (AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model (AG, OR=0.72, 95%CI 0.43-1.19, P=0.02; AA, OR=2.71, 95%CI 1.00-7.42; P=0.03). However, in three inherited models (dominant model, recessive model, and codominant model), none of the assayed loci was significantly associated with the prognosis of septic shock. The non-survivor group demonstrated higher plasma IL-6 levels (99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/mL, AG 85.4±43 pg/mL, and GG 65.3±30.7 pg/mL (P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were significantly higher than those in patients with GG genotypes (P<0.01). CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.

[Relation between level of expression of high mobility group protein B1 in hepatic tissue with the severity and prognosis of sepsis in rat].

OBJECTIVE: To investigate whether the levels of expression of high mobility group protein B1 (HMGB1) in hepatic tissue are related with severity and prognosis of sepsis in rat, in order to look for a dependable marker for monitoring and evaluating the efficiency of the treatment of sepsis. METHODS: Ninety SD rats (specific-pathogen free, male, 250-300 g) were randomly divided into sham operation group (group A), cecal ligation and puncture (CLP) group (group B) and CLP followed by ethyl pyruvate (EP) treatment group (group C). Laparo fury was done aseptically, and the cecum was returned to the abdomen (group A) or CLP was carried out (group B and C). The abdominal wall was then closed layer by layer. Normal saline (NS) 2 ml (group A and B) or EP 2 ml (130 mg/kg, group C) was intraperitoneally injected and repeated every 12 hours. Five animals were sacrificed at 0, 6, 12, 24, 48 and 72 hours after the operation, blood samples and 100 grams of hepatic tissue were harvested before the animal died. Before sacrifice, activity, food taking, piloerection, diarrhea, anophthalmia, respiration, distention of intestine, hyperemia, ascites, and omental adhesion to the cecum, and hyperemia of lung were observed. Another group of 20 rats were used to observe the survival rate after CLP. The level of HMGB1 mRNA expression in the hepatic tissue was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), and the levels of interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in plasma were determined by enzyme linked immunoadsorbent assay (ELISA). RESULTS: The mortality of sepsis was higher in group B than other groups (both P<0.01), that of group C was significantly lower than B but higher than A (both P<0.01). The levels of IL-1 beta, IL-6 and TNF-alpha in plasma rose to the peak at 6 hours after CLP in all groups, and group B>group C>group A (P<0.01), and they descended at 12 hours. The HMGB1 mRNA expression level in hepatic tissue was measurable at 6 hours and rose at 12 hours in group B, and maintained a high level up to 48 hours after CLP. The HMGB1 expression was positive correlated with IL-6 (r=0.91). The value in group C was significantly lower than group B at all time points (all P<0.01). The degree of severity and survival rate of sepsis were highly correlated with HMGB1 levels. CONCLUSION: As a late-released inflammatory mediator, HMGB1 plays a key role in lethal effect of sepsis, the surviving time and the severity degree of sepsis are highly correlated with HMGB1 expression level in hepatic tissue.

[Clinical study on effects of ulinastatin on patients with systemic inflammatory response syndrome].

OBJECTIVE: To evaluate the value of ulinastatin in hindering systemic inflammatory response syndrome (SIRS) to proceed to multiple organ dysfunction syndrome (MODS). METHODS: Sixty patients were randomly divided into routine treatment group (n=30) and ulinastatin treatment group (n=30). Both groups were given routine treatment, while the patients of the ulinastatin treatment group were given ulinastatin (100 kU intravenously drip, once every 8 hours, and continued for 5 days) in addition. Additionally, 15 healthy persons were enrolled as normal control group. Temperature (T), heart rate (HR), respiration rate (RR) and white blood cell (WBC) count were observed everyday. The duration of SIRS, the number of organ dysfunction, and mortality were also compared. Serum C reactive protein(CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6(IL-6) and IL-10 levels were measured before treatment and 5 days after in ulinastatin treatment group, routine treatment group, and in normal control group at the time of health examination. RESULTS: All of the SIRS markers were not different both in ulinastatin group and routine treatment group before treatment. T, RR, HR and WBC were reduced significantly after 3 days in ulinastatin groups(P<0.05 or P<0.01), but HR was not lowered significantly after 5 days and WBC after 7 days of treatment in regular treatment group (P<0.05 or P<0.01). All of the cytokines in ulinastatin treatment group and routine treatment group were higher than normal control group before treatment. Serum CRP, TNF-alpha and IL-6 levels were reduced significantly after 5 days of treatment in both ulinastatin treatment group and routine treatment group(P<0.01), but in ulinastatin treatment group the reduction was faster than routine treatment group(both P<0.01). IL-10 level was elevated significantly after treatment in ulinastatin treatment group(P<0.01), but it showed no significant change in routine treatment groups(P>0.05). The number of patients with duration of SIRS longer than 3 days were fewer and the incidence of MODS was lower in ulinastatin treatment group than those in routine treatment group(10.00% vs. 36.67%, P<0.05), and the fatality rate was reduced significantly with ulinastatin(3.33% vs. 20.00%, P<0.05). CONCLUSION: Ulinastatin significantly improves the inflammatory symptom and signs of SIRS, such as T, HR, RR, and WBC, inhibits the production of inflammatory cytokines, and enhance the anti-inflammatory cytokines in the treatment of SIRS. It can effectively prevent SIRS to proceed to MODS.