Vigário Ana Margarida, Belnoue Elodie, Grüner Anne Charlotte, Mauduit Marjorie, Kayibanda Michèle, Deschemin Jean-Christophe, Marussig Myriam, Snounou Georges, Mazier Dominique, Gresser Ion, Rénia Laurent
Institut Cochin, Département d'Immunologie, Paris, France.
J Immunol. 2007 May 15;178(10):6416-25. doi: 10.4049/jimmunol.178.10.6416.
Most C57BL/6 mice infected i.p. with Plasmodium berghei ANKA (PbA) die between 7 and 14 days with neurologic signs, and the remainder die later (>15 days) with severe anemia. Daily i.p. injections of a recombinant human IFN-alpha (active on mouse cells) prevented death by cerebral malaria (87% deaths in the control mice vs 6% in IFN-alpha-treated mice). The mechanisms of this IFN-alpha protective effect were multiple. IFN-alpha-treated, PbA-infected mice showed 1) a marked decrease in the number of PbA parasites in the blood mediated by IFN-gamma, 2) less sequestered parasites in cerebral vessels, 3) reduced up-regulation of ICAM-1 expression in brain endothelial cells, 4) milder rise of blood levels of TNF, 5) increased levels of IFN-gamma in the blood resulting from an increased production by splenic CD8+ T cells, and 6) fewer leukocytes (especially CD8+ T cells) sequestered in cerebral vessels. On the other hand, IFN-alpha treatment did not affect the marked anemia observed in PbA-infected mice. Survival time in IFN-alpha-treated mice was further increased by performing three blood transfusions over consecutive days.
大多数经腹腔注射感染伯氏疟原虫ANKA株（PbA）的C57BL/6小鼠在7至14天内死于神经症状，其余小鼠（>15天）死于严重贫血。每天腹腔注射重组人干扰素α（对小鼠细胞有活性）可预防脑型疟疾死亡（对照小鼠死亡率为87%，干扰素α治疗组小鼠死亡率为6%）。这种干扰素α保护作用的机制是多方面的。经干扰素α治疗、感染PbA的小鼠表现出：1）由干扰素γ介导的血液中PbA寄生虫数量显著减少；2）脑血管中被隔离的寄生虫减少；3）脑内皮细胞中ICAM-1表达上调减少；4）血液中TNF水平升高较轻；5）由于脾CD8+T细胞产生增加导致血液中干扰素γ水平升高；6）脑血管中隔离的白细胞（尤其是CD8+T细胞）减少。另一方面，干扰素α治疗并未影响感染PbA小鼠中观察到的明显贫血。通过连续三天进行三次输血，干扰素α治疗组小鼠的存活时间进一步延长。
