Intensive Insulin Therapy On Inflammatory Cytokines In The Patients With Severe Trauma

Objective:"Stress" hyperglycemia post trauma may be associated with increase mortality and poor prognosis in critical illness.Control of serum glucose with intensive insulin therapy may improve the prognosis for critical patients. Adverse outcomes of the severe injuries are often caused by systemic inflammation and unbalanced immune function,which contribute to increasing infection and SIRS.Pro-inflammatory cytokine,TNF-αand IL-6,as well as CRP and late- inflammatory cytokine,HMGB1,provoke inflammatory cascade post trauma.Intensive insulin therapy showed a powerful anti-inflammatory effect which at least partially explains improvement in morbidity and mortality.However, the mechanism of insulin therapy on anti-inflammatory effect post trauma is unclear.Study here would be to evaluate the effect of intensive insulin therapy on inflammatory response,serum lipoprotein,and HLA-DR.Methods:Insulin therapy directed at establishing euglycemia was investigated in sICU injured patients ISS＞20,tailored to control blood glucose levels in the range 8mmol/L,whereas the conventional treatment group only received insulin when glucose levels exceeded 11.1 mmol/L.Blood samples were obtained at 0,2,4,6 and 8 days after admission.ELISA assay was used to determine the expressions of TNF-α,HMGB1,IL-6 in protein and mRNA levels, and the levels of the immunological markers such as IgA,IgG,IgM,C3,C4 and acute reactive protein CRP post trauma in both intensive and routine groups. Two-color flow cytometric(FCM) analysis was used for the detection of the human leukocyte antigen HLA-DR expression on CD14~+ monocytes.Organ functions were assessed by APACHEⅡScore counted continually in first week.Results:(1) In comparison with control group,insulin therapy induced a slightly higher incidence of hypoglycemia.Insulin therapy may effectively prevent complications such as renal failure,liver dysfunction,hypoalbuminemia, and also reduce the APACHEⅡScore.(2) Within the 8 days post trauma,there were significantly lower levels of pro-inflammatory cytokines such as HMGB1,TNF-α,IL-6 and CRP,as well as serum lipoproteins levels such as TG,CH HDL and LDL,than that in control groups after one week post trauma. Serum and cells mRNA levels of HMGB1,TNF-α,IL-6 and NFκB in intensive insulin therapy group were significantly lower than that in controls.(3) Intensive insulin therapy may increase the levels of immunoglobulins and addiments such as C3 and C4.(4) Intensive insulin therapy may improve Monocyte HLA-DR expressing rates((P＜0.05或P＜0.01),and has no effect on CD14+ cells.Conclusions:Intensive insulin therapy effectly inhibits inflammatory cytokines by blood glucose control and protects organ functions post trauma and improves immunity,and by attenuating the systemic inflammatory response,may contribute to the improved prognosis of sever trauma.