甲型H1N1流感合并肺炎患者外周血中细胞因子、C反应蛋白、T淋巴细胞计数的动态分析

Dynamic Analysis of Peripheral Cytokines,C-reactive Protein,and Lymphocyte Counts in H1N1 Flu Patients with Complicated Pneumonitis

目的探讨合并肺炎的甲型H1N1流感患者血浆中相关细胞因子、C反应蛋白(CRP)及T淋巴细胞计数在病程中的变化特征,为临床早期诊断与治疗提供参考。方法检测16例合并肺炎的住院甲型H1N1流感患者血浆中相关细胞因子[γ干扰素(IFN-γ),白细胞介素6(IL-6),白细胞介素8(IL-8),肿瘤坏死因子-α(TNF-α),转化生长因子-β1(TGF-β1)]水平、CRP及T淋巴细胞计数的变化。根据患者入院时血气分析中动脉血氧分压(PaO2)水平,分为重症组(PaO2<60 mm Hg)9例与轻症组(PaO2≥60 mm Hg)7例;另设健康对照组8例。结果治疗前后(发病第7天、14天采血样),各组IFN-γ,IL-6,IL-8,TNF-α等水平变化无统计学意义(P>0.05),各组间差异亦无统计学意义(P>0.05)。治疗前重症组TGF-β1水平较轻症组明显增加,差异有统计学意义(P<0.05),治疗后重症组TGF-β1仍维持较高水平,与治疗前相比差异无统计学意义(P>0.05),部分病例在恢复期(体温正常,气短减轻,血氧正常)发现肺纤维化征象。CRP水平的升高与低淋巴细胞血症在重症组和轻症组均常见,但重症组治疗前淋巴细胞总数更低,与轻症组相比差异有统计学意义(P<0.05);治疗后,两组低淋巴细胞血症明显改善,与治疗前相比差异均有统计学意义(P<0.05),CRP水平的明显下降仅见于轻症组,差异有统计学意义(P<0.05)。所有幸存者的CRP水平与淋巴细胞总数均迅速地恢复至正常,相反,治疗后CRP水平无明显下降者及淋巴细胞总数无明显上升者预后较差。结论通过对血浆相关细胞因子水平(IFN-γ,IL-6,IL-8,TNF-α,TGF-β1)的测定发现,合并肺炎的甲型H1N1流感病例血浆中,只有TGF-β1是过度产生的;其他细胞因子水平无变化的原因可能与大部分入选病例使用糖皮质激素有关,糖皮质激素可抑制机体针对甲型H1N1流感病毒感染的免疫反应。治疗前血中TGF-β1水平、T淋巴细胞总数与疾病严重性有关,可能对疾病严重性有预测作用。血中升高的TGF-β1水平与甲型H1N1流感合并肺炎患者肺纤维化的发生之间的关系仍需进一步研究。

Objective To explore the changes of plasma cytokines,C-reactive protein（CRP）,and lymphocyte counts in H1N1 patients with complicated pneumonitis and to provide reference for early diagnosis and early treatment. Methods Changes of plasma cytokines[interferon γ（IFN-γ）,interleukin 6（IL-6）,interleukin 8（IL-8）,transforming necrosis factor α（TNF-α）,transforming growth factor β1（TGF-β1）],C-reactive protein（CRP） and T cell counts in 16 hospitalized H1N1 patients with complicated pneumonitis were investigated.These patients were classified as severe（PaO260 mm Hg,9 cases） and mild（PaO2≥60 mm Hg,7 cases） according to partial pressure of oxygen at admission.Eight healthy medical professionals were enrolled as controls. Results Cytokine profiles showed no changes in IFN-γ,IL-6,IL-8,and TNF-α levels throughout the observation period（P0.05）as well as among groups（P0.05）.TGF-β1 was significantly higher in the severe group than in the mild group before treatment（P0.05） and no significant differences were noted after treatment（P0.05）.Signs of pulmonary fibrosis including normal body temperature,alleviated short breath,and normal PaO2 were noted in some cases during the recovery period.Elevated CRP levels and lymphopenia were common in both the severe and the mild group.Lymphocyte counts in the severe group were significantly lower than in the mild group before treatment（P0.05） while after treatment,a noticeable elevation in lymphocyte count was noted in both groups（both P0.05）.CRP decrease was merely seen in the mild group（P0.05）.Lymphocyte counts and CRP levels rapidly recovered to normal levels in all survivors after treatment;otherwise the patients would end up with poor prognosis. Conclusion Serial measurements of cytokines shows that only TGF-β1 is overproduced,possibly due to the early use of corticosteroids,which may have down-regulated the immune responses to H1N1 infection.Pretreatment plasma TGF-β1 concentrations and absolute lymphocyte counts are possible predictors of severity.However,the role of elevated TGF-β1 levels in H1N1 infection-associated pulmonary fibrosis requires further investigation.