| Objective:Through the detection of the dynamic changes between pro-inflammatorycytokines and anti-inflammatory cytokines, which are existed in the blood serum ofthe patients with HBV infection, the pathogenesis of severe Hepatitis B was exploredand the significance of predicting clinical prognosis was discussed according to thechanges.Methods:37patients were divided into three groups the fast recovery group, the slowrecovery group and the treatment failure group, which based on clinical symptomsand signs, coagulation, liver function recovery time. Meanwhile, there were20patients with mild liver damage as control groups. Adopting Enzyme-linkedImmunosorbent Assay (ELISA) was used to determine the base line, treatment for1week, paracmasis or critical stage、1day prior to discharge serum levels ofpro-inflammatory cytokines: IL-12, IL-17, IL-1beta, IFN-gamma, TNF-alpha andanti-inflammatory cytokine IL-10, TGF-β, IL-35’s level. Compare with the dynamicchanges of the different groups before and after treatment on cytokine levels.Results:1. When the severe liver was injured,serum levels of TNF-alpha in fast recoverygroup, slow recovery group, treatment failure group, the control group were63.76±27.84(pg/ml),107.7±54.92(pg/ml),118.19±38.09(pg/ml),16.43±2.81(pg/ml);IL-12levels were80.48±58.47(pg/ml),(121.46±39.27pg/ml),131.51±87.58(pg/ml),32.81±16.78(pg/ml); IL-17levels were111.55±40.05(pg/ml),143.46±36.25(pg/ml),160.58±41.56(pg/ml),35.50±33.97(pg/ml); IFN-γlevels were246.2±92.14(pg/ml),360.41±96.53(pg/ml),412.06±139.9(pg/ml),64.11±15.48(pg/ml); IL-1βlevels were290.39±55.58(pg/ml),395.19±26.7(pg/ml),449.78±118.4(pg/ml),56.84±24.79(pg/ml). Performance: treatment failure group>slowrecovery group>fast recovery group>control group， there were no statistical differences between treatment failure group and slow recovery group (P>0.05);(P<0.05) has obvious differences between pairwise comparisonb.2. When the severe liver was injured, serum levels of IL-10in fast recoverygroup, slow recovery group, treatment failure group, the control group were104.84±28.02(pg/ml),27.59±6.32(pg/ml),29.25±3.21(pg/ml),(48.72±2.64pg/ml).The slow recovery group and the treatment recovery group is less than fast recoverygroup and the control group (P <0.05); the slow recovery group and the treatmentfailure group have no statistically significant (P>0.05); TGF-β contents were170.97±71.38(pg/ml),127.63±28.98(pg/ml),39.91±8.53(pg/ml),87.96±28.31(pg/ml), fast recovery group> slow recovery group> control group> treatment failuregroup, and the comparisons between each of them were statistically significant (P <0.05);serum levels of IL-35were314.02±120.18(pg/ml),287.03±39.95(pg/ml),270.37±18.79(pg/ml),102.67±49.35(pg/ml), the performance is that fastrecovery group> slow recovery group> treatment failure group> control group, butthe comparisons of those three have no significant difference (P>0.05) in fastrecovery group, recovery group and treatment failure.3. The dynamic changes of the pro-inflammatory cytokines: a. In fast recoverygroup, the level of pro-inflammatory cytokines has been a downward trend:admission>1week of treatment> discharge, and the comparison of different time hasstatistically significant (P <0.05). b. In slow recovery group, the level changes ofpro-inflamm atory cytokines IL-17, IL-1β, IFN-γ, TNF-α:1week after treatment>admission, the comparison has statistically significances(P <0.05); IL-12levelis:after one week of treatment <admission, those two has no statisticalsignificances(P>0.05); In the paracmasis, the levels of all pro-inflammatorycytokines are decreased:1week after treatment>paracmasis>discharge, which hasstatistical significances (P <0.05). c. In treatment failure group: pro-inflammatorycytokines IL-12, IL-17, IFN-gamma, TNF-alpha has been rising: discharge> criticalperiod>1week after treatment> base line, the comparison between both of them hasstatistically significant (P <0.05); the changes of IL-1β: the critical period>1week aftertreatment>base line it has obvious differences between both of them(P <0.05),discharge <the critical period, but it has no statistical significances (P>0.05), and it is still at a high level.4.The dynamic changes of the anti-inflammatory cytokine: a. In fast recoverygroup:The levels of three kinds of anti-inflammatory cytokine were peak after1week of treatment then dropped to a low level at discharge:base lines<after1week oftreatment、after1week of treatment<discharge，P <0.05compared with each other。b. chronic recovery group：IL-10and TGF-beta performance: paracmasis>1weekafter treatment>baseline (P <0.05)，but the discharge performance of different：IL-10is discharged <remission (P <0.05), and TGF-beta concentration continues to rise atdischarge> remission (P <0.05); IL-35performance for1week after treatment<baseline (P>0.05), remission <1week of treatment (P <0.05), discharge> remission(P>0.05)。c. treatment failure group：IL-10performance baseline>1week aftertreatment> critical period> discharge, comparison was statistically significant (P<0.05); TGF-beta performance baseline>1week after treatment, critical period> after1week treatment, critical period> discharge, but pairwise comparisons were nosignificant (P>0.05); level of IL-35was a slight increase baseline <1week aftertreatment <critical period <discharged, but is still in low level state, and before andafter were not statistically significant (P>0.05).Conclusions:1. All the serum levels of pro-inflammatory cytokines IL-12, IL-17, IL-1β, IFN-γ,TNF-α elevated in the initial stage of patients with severe liver injuried caused byHBV.The serum levels of pro-inflammatory cytokines were significantly high in slowrecovery group and treatment failure group high compared with the fast recoverygroup,The results indicate pro-inflammatory cytokines can clear virus but also causeliver damage, the higher of pro-inflammatory cytokines, the more severe liver damage.The levels of anti-inflammatory cytokines also affect the degree of liver injury, thehigher the initial anti-inflammatory cytokines,the lighter liver damage and easier torecover.2. The dynamic changes of pro-inflammatory cytokines and anti-inflammatorycytokines wouldl affect disease outcomes: on the condition of the anti-inflammatorycytokine (IL-10and TGF-β) levels increasing and the inflammatory cytokines levelsdecreasing or in a lower level, the patient’s condition is getting better (fast recovery group and slow recovery group), while, if the pro-inflammatory cytokines continuedto be in a high level and with no significant decrease, the anti-inflammatory cytokineslevels was in a low level and with no significant increase, the patient’s condition mayexacerbate or cause delayed healing (treatment failure group). After conditionimproved high levels of anti-inflammatory cytokine TGF-beta connect with liverfibrosis. Therefore, the dynamic changes between the two will determine the finaloutcome of the disease. |
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