| Part I Clinical ObservationArticle 1 Pro- versus anti-inflammatory and HPA axis profiles in patients with severe sepsis : The relationship with prognosis andhemodynamic changesTo investigate whether the pro-/anti-inflammatory response and neuroendocrine profile in the circulation is associated with adverse outcome and early hemodynamic change in severe sepsis. Serum concentration of the proinflammatory cytokine tumor necrosis factor (TNF)-a and the anti- inflamma tory cytokine interleukin(IL)-10, prostaglandin (PG)E2, and adrenocorti- cotropic hormone (ACTH), cortisol (Cor), β-endorphine (β-EP) were measured in 20 patients with severe sepsis resulting from intra-abdominal infection during the first 48 hours after admission. T helper (Th) subset and surface expression of HLA-DR on monocytes were also measured by flow cytometry. All patients were evaluated clinically for acute physiologic score and followed up for outcome. Levels of both pro- and anti-inflammatory cytokines and HPA axis hormones were significantly elevated in patients, the Th1 cells were significantly lower while Th2 higher than controls and Th1:Th2 ratio decreased, the HLA-DR expression in sepsis patients were only 32% of controls. Higher levels of TNF- a , PGE2, ACTH, 3 -EP, Th1:Th2 ratio and lower Cor were detected in early sepsis shock patients, whereas elevated levels TNF-a JL-10, PGE2, ACTH, Cor and alow TNF-a to IL-10 ratio were associated with death and remained during 48 houes, the ratio of Th1:Th2 and expression of HLA-DR were remained lower in nonsurvivors, whereas IL-10, Th1:Th2, HLA-DR paralleled the APS. These results show that both the inflammatory and anti-inflammatory response are profoundly augmented in early stage of severe sepsis, the sustained of overreaction of anti-inflammatory such as IL-10, shifting of Th subsets to Th2, and hyporesponse of monocytes are related with severity and fatal outcome, the high level of TNF-a, PGE2,β-EP and the adrenal insufficiency will predict an early hemodynamic deterioration.Article 2 The effects of Dachengqi Grannie on pro-/anti-inflammatory balance and neuroendocrine functions in patientswith severe sepsisTo investigate the therapeutic effects of Dachengqi Granule(DG), a Chinese traditional medicinal prescription on prq-/anti-inflammatory response and HPA axis profile in patients with severe sepsis. Serum concentration of the pro inflammatory cytokine TNF-a and the anti-inflammatory IL-10, PGE2, and ACTH, Cor, 3 -EP were measured in 12 patients with severe sepsis resulting from intra-abdominal infection during 6 days after admission and compared with control. Th subset and HLA-DR expression on monocytes were also measured. The restore of both pro-/anti-inflammatory cytokines and HPA axis hormones were significantly better hi patients treated with DG, in which IL-10 declined after 48 hours after admission and higher TNF-a to IL-10 ratio was also found at same time. The ratio of Th1 :Th2 and expression of HLA-DR were higher after DG giving, whereas HLA-DR at 4 days after admission and Th subset in 6 days. These results show that DG has inhibiting function for overproduction of proinflammatory cytokine TNF-a , and also has effects on anti-inflammatory IL-10 and HPA axis hormones, it has even facilitate Th subsets and HLA-DR expression, in therapeutic mechanism is multitarget and complex.Part II Cell CultureArticle 1 Change of monocyte responsiveness and influencing factors in patients with severe sepsisTo study the pattern of cytokines release in peripheral blood mononuclear cells (PBMC) in patients with severe sepsis and to determine the role of IL-10 and endogenetic glucocoticoid in monocyte hyporesponsiveness during severe sepsis and the influence of Chinese traditional medicines (CTM). First, PBMC isolated from 11 patients with severe sepsis and 7 healthy controls were intubated with or without lipopolysaccharide (LPS) and cytokine release were assessed, Emodin and Shenmai injectio (SMI), two CTM were used in cell culture. Next, normal PBMC were in...
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