| BackgroundSepsis is a common complication after the severe injury such as burn, shock, infection and major surgery operation. Sepsis is a syndrome caused by the infection of systemic inflammation response syndrome. If early stage of sepsis can not be cured, it can develop to sepsis shock and multiple organ dysfunction syndrome, even to multiple organ failure (MOF). MOF is the major cause of high mortality of critical patients. Sepsis is caused by infection in etiology and threat the healthy of human in pathophysiology. Sepsis is understood gradually in the long period clinical practice. A great effort has been done to enhance the therapeutic effect and decrease the morbidity and the mortality of sepsis and MODS. The mechanism of sepsis and MODS is complicated, both environmental and genetic factors contribute to the pathogenesis of sepsis. During this process the inflammatory factor play the critical roles and the ascent and decrease of inflammatory factor will influence the outcome of sepsis. Among the major inflammatory IL-6 play the important roles in process of sepsis and MODS. IL-6 is a multifunctional cytokine with a central role in host defense, has diverse functions including stimulation of the hepatic acute phase response to infection and injury, differentiation and/or activation of macrophages and T cells, growth and terminal differentiation of B cells, and induction of fever. Several clinical studies provide evidences that plasma levels of IL-6 closely correlate with the severity and outcome of sepsis, suggesting a pathogenic role of IL-6. Many factors can influence IL-6 expression, the systemic concentrations of IL-6 are mainly regulated at the level of expression, because IL-6 is rapidly cleared from the plasma. The clinical practices disclose that IL-6 expression keep on at high level in severe patients. This result is regulated by the gene level. There are several single nucleotide polymorphisms in IL-6 gene promoter region. Several experiments in vitro testify the allele in the SNP of IL-6 promoter associate with the concentration of IL-6. The allele in the SNP of IL-6 can influence and regulate the IL-6 expression thus decided the outcome and onset of several diseases. IL-6 is not constitutively expressed but is highly inducible and is produced in response to a number of inflammatory stimuli such as IL-1, platelet-derived growth factor, tumor necrosis factor-α(TNF-α), bacterial products such as endotoxin, and viral infection. Glucocortocoids produced as part of the inflammatory response act to enhance some IL-6 effects, such as acute phase protein synthesis, but down-regulate IL-6 expression, providing a negative feedback pathway on the inflammatory response in vivo. Many cell types produce IL-6 in response to noxious stimuli, including monocytes/macrophages, fibroblasts, endothelial cells, adipocytes, T cells, and mast cells. All these cells were influenced by many factors when they express IL-6.AimThe aim of this study is to investigate the concentration of IL-6 in plasma in sepsis patients and controls and ascent or descent of concentration IL-6 in the different phase of sepsis. At the same time to investigate the difference of IL-6 concentration between the different severities of sepsis and to explore whether IL-6 can be a signal of prognosis of sepsis. Genotype was performed to explore the initial mechanism of sepsis. Single nucleotide polymorphism of IL-6 -174 and -572 in promoter of IL-6 were investigated to understand the regularity of sepsis and susceptibility of sepsis and MODS.Materials and MethodsThe objects come from the first affiliated hospital of Zhengzhou university. All the subjects are common residents of Henan province and the place of birth belong to Henan province. The sepsis patients 99 cases include common sepsis 37, severe sepsis 30, sepsis shock 16 and MODS 16. Healthy controls are 216. All the subjects of sepsis diagnosis and severity grade according to ACCP/SCCM. Patients were excluded from this study when at least one of the following criteria was fulfilled:age<18yrs or>75yrs, pregnancy ,organ transplantation , hepatic cirrhosis, hematological system disease, chronic organ dysfunction and applied immunosuppressive agent, and carcinoma, chronic inflammatory disorders.The severity is evaluated by APACHE. ELISA if performed to detect the concentration of IL-6 of serum .PCR-RFLP is used to judge the genotype of IL-6-174 and -572.ResultsThere is significant difference of IL-6 concentration between sepsis patients and controls (P<0.05). The concentration of IL-6 decreased as time gone by. The expression of IL-6 level in the MODS and no-MODS has significant difference at the 3,5,7,14th day and at the 5,7th day there is significant difference between MODS group and no-survival group. In the IL-6-174 there was only GG genotype, however there were GG, GC, CC genotype in the IL-6-572. All the subjects genotype distributions of patients and controls were in Hardy-Weinberg equilibrium (P>0.05) for IL-6-572.There was no significant difference of allele frequency between patients and controls. The associations with the susceptibility to sepsis were estimated by logistic regression at IL-6-572.We observed a statically increase susceptibility to the sepsis associated with homozygous alleles G (assigned as GG genotype, odds ratio [OR]=2.411,95% confidence interval [CI]=1.045- 5.562,P=0.039) compared with the homozygous alleles C after adjusting for sex and age. Subset of sepsis is common sepsis and critical sepsis (Include severe sepsis, sepsis shock, MODS).There were marginal significant association with the severity of two groups for IL-6-G572C SNP.Conclusions1. IL-6 can as a sensitive index of severity and prognosis of sepsis and MODS.IL-6 can long period and high concentration express in the critical patients.2. IL-6-G-572C SNP associates with sepsis and MODS genesis.GG genotype is the risk genopype of sepsis.3. IL-6-G572C SNP associates with sepsis and MODS (marginal significance) 4. There maybe no SNP in II-6-G174C in Henan population in china. |
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