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The expression of the cytokines IL-2, IL-10, TNF-α and their roles in mice with herpes simplex viral encephalitis (HSE) were studied. By using semiquantitative reverse transcription polymerase chain reaction (RT-PCR), the expressions of IL-2, IL-10 and TNF-α mRNA in control group, HSE group and acyclovir (ACV)-treated group were detected and the pathological changes of brain were observed. It was found that after HSV1 infection, the cerebral lesions of haemorrhage and necrosis in mice were observed under the microscopy, and the levels of IL-2, IL-10 and TNF-α were increased remarkably. After treatment with ACV after HSV1 infection, the cerebral lesions in mice were improved, the level of IL-2 maintained stable, IL-10 was increased consistently, and TNF-α was decreased significantly as compared with those in HSE group. In acute HSE, many cytokines are upregulated, including IL-2, IL-10 and TNF-α to eliminate virus and TH1 type response is dominant. In convalescence, there is a shift in the cytokine expression profile from TH1 profile to TH2 profile and the shift can inhibit the overexpression of immune response in animals. ACV has remarkable effects in the treatment of HSE.