Muniz-Junqueira Maria Imaculada, Silva Forland Oliveira, de Paula-Júnior Milton Rego, Tosta Carlos Eduardo
Laboratory of Cellular Immunology, Department of Pathology, Faculty of Medicine, University of Brasilia, 70910-900 Brasilia, DF, Brazil.
Acta Trop. 2005 May;94(2):128-38. doi: 10.1016/j.actatropica.2005.03.002. Epub 2005 Apr 7.
Malaria remains a major cause of morbidity and mortality in vast areas of the world, mainly due to the severe forms of Plasmodium falciparum infection. The exacerbated immune response, with increased production of TNF and reactive nitrogen and oxygen intermediates, plays a role in the complex pathogenesis of the disease. It is recognised that thalidomide decreases TNF production and may modulate several functions of the immune system. This work evaluated the influence of thalidomide on macrophage functions, and its ability to protect against severe disease. Plasmodium berghei ANKA-infected mice were (n=11) or were not (n=10) intra-gastric treated with thalidomide (150 mg/kg per day), and two other control groups not infected with the parasite were (n=8) or were not (n=10) treated with the drug, and macrophage production of hydrogen peroxide and nitric oxide, and phagocytosis were assessed on the eighth day post-infection. Thalidomide increased the survival time of infected mice, in parallel with a 26.5% increase of the mean of macrophage phagocytic index, and augmented in 13% the mean of the production of hydrogen peroxide and in 45% the mean of nitric oxide production by macrophages related to the non-treated P. berghei-infected mice. Our data indicate that thalidomide improves the outcome of P. berghei ANKA-infected CBA mice and suggest that this drug could represent a new alternative to be associated to antimalarial drugs to decrease the morbidity and mortality of severe malaria in non-pregnant individuals.
疟疾仍然是世界上广大地区发病和死亡的主要原因，主要是由于恶性疟原虫感染的严重形式。加剧的免疫反应，伴随着肿瘤坏死因子（TNF）以及活性氮和氧中间体产生的增加，在该疾病复杂的发病机制中发挥作用。众所周知，沙利度胺可降低TNF的产生，并可能调节免疫系统的多种功能。这项研究评估了沙利度胺对巨噬细胞功能的影响及其预防严重疾病的能力。将感染伯氏疟原虫ANKA的小鼠（n = 11）或未感染的小鼠（n = 10）用沙利度胺（每天150 mg/kg）进行胃内治疗，另外两个未感染寄生虫的对照组（n = 8）或未接受药物治疗的对照组（n = 10），在感染后第8天评估巨噬细胞产生过氧化氢和一氧化氮的情况以及吞噬作用。沙利度胺延长了感染小鼠的存活时间，同时巨噬细胞吞噬指数的平均值增加了26.5%，与未治疗的感染伯氏疟原虫的小鼠相比，巨噬细胞产生过氧化氢的平均值增加了13%，一氧化氮产生的平均值增加了45%。我们的数据表明，沙利度胺改善了感染伯氏疟原虫ANKA的CBA小鼠的预后，并表明这种药物可能是一种新的选择，可与抗疟药物联合使用，以降低非孕妇严重疟疾的发病率和死亡率。
