Th1/Th2细胞因子在感染中的意义 浙江大学附属儿童医院 宁铂涛

细胞因子 由免疫系统细胞以及其他类型细胞主动分泌的一类小分子量的可溶性蛋白质。包 括淋巴因子、干扰素、白介素、肿瘤坏死因子、趋势化因子和集落刺激因子等。 是免疫系统细胞间，以及免疫系统细胞与其他类型细胞间联络的核心，通过与细 胞特异的膜受体相互作用，能改变分泌细胞自身或其他细胞的行为或性质。

The differentiation of naïve T cells to Th cells The differentiation of naïve T cells to Th cells. Depending on the adjuvanticity of the substances co-exposed with the antigen and status of the cells and cytokines in the microenvironment, naïve T cells can differentiate into Th1, Th2, Th9, Th17, and Th22. 

Role of Th1 and Th2 cells, and cytokines in the regulation of cellular and humoral immunity.

Th1/Th2 profile in our hospital

IL-2, IL-4, IL-6, IL-10, TNF-a and IFN-r in the sera. the cytometric bead assay (CBA) Human Th1/Th2 Cytokine kit II (BD Biosciences, San Jose, CA, USA).

Results from current data

During infection and infection controlled

The median levels of IL-4, IL-6, IL-10, TNF-a and IFN-r in febrile patients before antibiotic therapy were 3.9, 660.1, 122.7, 6.9 and 11.4 pg/mL, respectively. The interval between the two detections was 5.5 (2–24) days. Returned to 3.3, 22.8, 9.6, 4.1 and 6.4 pg/mL, respectively, after infection was controlled.

Between the G+ and G− Bacterial Sepsis

IL-6, IL-10, and TNF-a levels in patients with G− bacterial infection were higher than those in patients with G+ bacterial infection. The IL-6, IL-10, and TNF-a of G− group were 525.4 (10.2 to >5,000), 96.0 (7.0 to >5,000), and 6.9 (2.5–4263.4) pg/ml, respectively, which were all significantly higher than those of G+ group (150.0 (8.5 to >5000), 22.6 (3.4–2813.7), and 4.5 (2.5–81.6) pg/ml (P<0.001), but the IL-2, IL-4, and IFN-r levels were comparable between the two groups (P>0.05).

In Hemophagocytic Lymphohistiocytosis (HLH)

In HLH patients, IFN-r and IL-10 levels were significantly elevated and IL-6 levels were moderately elevated, but in MDI patients, IL-6 levels were much higher (usually >1000.0 pg/mL) than in HLH patients (60/145 (41.4%) vs. 2/43 (4.7%); p <0.001); IL-10 levels were highly elevated in patients with HLH and MDI diseases, but the rate in HLH cases (21/43 (48.8%) with high levels of IL-10 (>1000.0 pg/mL)) was significantly higher than that (17/145 cases (11.7%); p <0.05) in MDI patients.

The IFN-r levels in the EBV and CMV infection groups were slightly higher than those in the bacterial infectious group, but no significant differences were identified statistically (p >0.05). IFN-r levels were only slightly increased in MDI patients, being rarely more than 100.0 pg/mL (8/145 (5.5%) vs. 39/43 (90.7%) in HLH patients; p <0.001).

Between septic shock and non-shock

In septic shock, the IL-2, IL-4, IL-6, IL-10, TNF-a and IFN-r levels were 3.2 (2.3–150.1), 4.7 (2.3–54.9), 2430.6(155.0–>5000), 418.9 (27.8–>5000), 6.5 (3.3–2140.7) and 10.5 (2.7–394.9) pg/mL, respectively; these levels were significantly higher than those (3.0 (1.0–13.5), 3.5 (1.0–39.3), 98.4(3.8–>5000), 20.4 (3.4–>5000), 4.5 (1.7–4263.4) and 10.1(1.8–834.1) pg/mL, respectively) (p <0.001) in the febrile episodes without septic shock.

When the IL-6 levels exceeded the maximum detection limits (>5000 pg/mL),the IL-10 levels exceeded 1000.0 pg/mL. The IL-6 and IL-10 levels were positively associated with septic shock and mortality rates. the neutropenia subgroup and the non-neutropenia subgroup had comparable cytokine levels (p >0.05), indicating that the absolute neutrophil (ANC) count did not affect the cytokine levels.

Cutoff values of 40. 6 pg/mL for IL-6, 20. 0 pg/mL for IL-10 and 4 Cutoff values of 40.6 pg/mL for IL-6, 20.0 pg/mL for IL-10 and 4.2 pg/mL for TNF-a might be important parameters for distinguishing patients with a high probability of having a bacterial infection from those with a low probability. To judge a severe infection, the cut-off values of IL-6, IL-10 and TNF-a can be set at 227.7, 42.0 and 4.6 pg/mL, respectively.

Further study Tang et al. Clinical Microbiology and Infection 2011;17(11):1666-1673. Tang et al. Pediatr Blood Cancer 2012; 58:50–54.

谢 谢 ！