MONOCLONAL-ANTIBODY AGAINST INTERFERON-GAMMA CAN PREVENT EXPERIMENTAL CEREBRAL MALARIA AND ITS ASSOCIATED OVERPRODUCTION OF TUMOR NECROSIS FACTOR
MONOCLONAL-ANTIBODY AGAINST INTERFERON-GAMMA CAN PREVENT EXPERIMENTAL CEREBRAL MALARIA AND ITS ASSOCIATED OVERPRODUCTION OF TUMOR NECROSIS FACTOR
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DOI：
10.1073/pnas.86.14.5572
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发表时间：
1989-07-01
影响因子：
11.1
通讯作者：
VASSALLI, P
中科院分区：
文献类型：
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作者：
GRAU, GE;HEREMANS, H;VASSALLI, P
实验性脑型疟疾（ECM）是一种致死性超急性神经系统综合征，与高血液肿瘤坏死因子水平相关，在遗传易感（CBA/Ca）小鼠感染伯氏疟原虫ANKA株后7天发生。注射抗重组鼠干扰素γ的中和性单克隆抗体，在感染后4d内，显著降低ECM的发生率和血清肿瘤坏死因子水平的升高。该处理防止了脑损伤（单核细胞、淋巴细胞和寄生红细胞堵塞脑血管）。相比之下，淋巴器官中巨噬细胞浸润的程度（这是小鼠发展ECM的特征性特征）以及感染过程保持不受抗体处理的影响。受保护的小鼠在随后的时间死于严重贫血和过度寄生虫血症，这是对ECM不敏感的小鼠中伯氏疟原虫感染的通常结果。 目前的数据表明干扰素γ构成了导致实验性疟疾脑血管炎症的细胞因子网络中的重要环节。提出干扰素γ.由活化的CD 4 +T细胞释放，通过增加肿瘤坏死因子的产生和作用起作用。
Experimental cerebral malaria (ECM), a lethal hyperacute neurological syndrom associated with high blood levels of tumor necrosis factor, develops in genetically susceptible (CBA/Ca) mice 7 days after infection with Plasmodium berghei ANKA strain. Injections of neutralizing monoclonal antibody against recombinant murine interferon .gamma., not later than 4 days after infection, markedly reduced the incidence of ECM and the elevation in serum levels of tumor necrosis factor. This treatment prevented the cerebral lesions (plugging of brain vessels by monocytes, lymphocytes, and parasitized erythrocytes). In contrast, the extent of macrophage infiltration in lymphoid organs (which is a characteristic feature of mice developing ECM), as well as the course of infection, remained unaffected by the antibody treatment. Protected mice died at a later time of severe anemia and overhwelming parasitemia, the usual outcome of P. berghei infection in mice that are not susceptible to ECM. The present data indicate that interferon .gamma. constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon .gamma. released by activated CD4+T cells acts by augmenting both production and action of tumor necrosis factor.