干扰素α-2a与α-2b的免疫原性研究

Immunogenicity on interferon α-2a and interferon α-2b

摘要:

目的：观察干扰素α-2a（interferon α-2a，IFNα-2a）与干扰素α-2b（interferon α-2b，IFNα-2b）对昆明小鼠的免疫原性与免疫毒性。方法：实验设阳性对照P组（环磷酰胺，cytoxan，CTX，200 mg/kg）、IFNα-2b高剂量组（A组，2 μg/mL）、IFNα-2b低剂量组（B组，0.5 μg/mL）、IFNα-2a高剂量组（C组，2 μg/mL）、IFNα-2a低剂量组（D组，0.5 μg/mL）以及阴性对照组（溶剂对照组，N组，0.1%牛血清蛋白Bovine serum albumin 0.1%BSA），每组8只腹腔注射给药5周。通过血清干扰素（interferon，IFN）浓度、干扰素抗体（antibodies of interferon，Anti-IFN）浓度及肾脏C3补体免疫组化进行免疫原性对比；通过小鼠体质量增量、脏器系数、血液学指标、免疫球蛋白以及脾脏组织病理学切片进行免疫毒性对比。结果：血清IFN浓度A组（9.27±0.79）高于C组（7.80±1.26）（P=0.000）；B组（7.91±1.09）高于D组（5.97±0.98）（P=0.013）。血清Anti-IFN浓度A组（7.49±1.30）低于C组（10.31±0.69）（P=0.000）；B组（6.18±1.02）低于D组（8.24±0.74）（P=0.013）。肾脏C3免疫组化A组（0.51±0.00）低于C组（0.54±0.00）（P=0.000）；B组（0.42±0.00）低于D组（0.47±0.00）（P=0.013）。体质量增长量A组低于C组（P=0.015）；B组低于C组（P=0.003）。脏器系数实验组与阴性对照组N组无差异。A、B、C、D组在白细胞计数（white blood cell count，WBC）、血小板计数（platelet count，PLT）、平均血红蛋白量（mean corpuscular hemoglobin，MCH）、淋巴细胞计数（lymphocyte count，LY）、淋巴细胞百分比（lymphocytes percentage，LY%）指标上高于N组但低于P组（P<0.05）。IgA、IgM、IgG浓度检测无统计学差异。干扰素实验组脾脏切片未发现病理结构改变。结论：IFNα-2a与IFNα-2b的免疫原性有差异；免疫毒性无明显差异。

Abstract:

Objective：To investigate the immunogenicity and the immunotoxicity of interferon α-2a（IFNα-2a） and interferon α-2b（IFNα-2b） on Kunming mice. Methods：Kunming mice were randomly divided into six groups（eight mice in each group）：positive control group（treated with cyclophosphamide，P group），IFNα-2b high dose group（A group），IFNα-2b low dose group（B group），IFNα-2a high dose group（C group），low dose group（D group） and negative control group（treated with solvent，N group）. Mice were treated by intraperitoneal injection for 5 weeks. The serum concentration of IFNα，antibodies of interferon（Anti-IFN） and the im－munostaining result of alexin C3 were determined to evaluate the immunogenicity effect. In addition，the body weight，organ index，hematologic traits and histopathological examination were determined to evaluate the immunotoxicity effect. Results：For the concen－tration of serum IFN，group A（9.27±0.79） was higher than group C（7.80±1.26）（P=0.000）；group B（7.91±1.09） was higher than group D（5.97±0.98）（P=0.013）. For the concentration of Anti-IFN，group A（7.49±1.30） was lower than group C（10.31±0.69）（P=0.000）； the group B（6.18±1.02） was lower than group D（8.24±0.74）（P=0.013）. For the kidney immunohistochemistry，group A（0.51±0.00） was lower than group C（0.54±0.00）（P=0.000）；group B（0.42±0.00） was lower than group D（0.47±0.00）（P=0.013）. For the weight gain，group A was lower than group C（P=0.015）；group B was lower than group C（P=0.003）. There was no significant difference between the experimental group and the N group when comparing the kidney index，liver index，and spleen index. Levels of WBC，PLT，MCH，and LY in group A，B，C and D were higher than those in the N group，and were lower than those in the group P（P<0.05）. There was no significant difference among the IgA，IgM and IgG in the immunoglobulin test results. There was no significant pathological change in spleen slices in the experimental group. Conclusion：There is significant difference between IFNα-2a and IFNα-2b for immunogenicity. Moreover，there is no significant difference between IFNα-2a and IFNα-2b for immunotoxcity.