Elased K M, Taverne J, Playfair J H
Department of Immunology, University College London Medical School, UK.
Clin Exp Immunol. 1996 Sep;105(3):443-9. doi: 10.1046/j.1365-2249.1996.d01-781.x.
Hypoglycaemia in falciparum malaria is associated with a poor prognosis and is correlated with mortality. High levels of serum TNF are also correlated with disease severity and mortality, and it has been suggested that TNF may cause the hypoglycaemia. However hypoglycaemia in mice infected with Plasmodium chabaudi or the lethal strain of P. yoelii YM is related to hyperinsulinaemia. Its development was not prevented by treatments which diminished TNF activity or production without affecting levels of plasma insulin. Conversely, it was inhibited by diazoxide, which inhibited insulin secretion but did not affect TNF production. Furthermore, in mice exhibiting neurological symptoms during infection with P. berghei, blood glucose concentrations were significantly raised when TNF levels were high, and TNF levels in the spleen were highest of all in non-lethal P. yoelii infections in which hypoglycaemia does not occur. Administration of human rTNF to normal animals caused an increase rather than a drop in blood glucose levels. Mice transgenic for human TNF did not develop hypoglycaemia when infected with P. yoelii YM, but showed signs of insulin resistance. In line with current views on the role of TNF in obesity and the control of glucose homeostasis, we conclude that the hypoglycaemia of malaria is not caused by increased levels of TNF, which may in fact be beneficial, but is secondary to a hyperinsulinaemia that is probably stimulated directly by products of the parasite.
恶性疟中的低血糖与预后不良相关，且与死亡率相关。血清肿瘤坏死因子（TNF）水平升高也与疾病严重程度和死亡率相关，有人提出TNF可能导致低血糖。然而，感染查巴迪疟原虫或约氏疟原虫致死株YM的小鼠发生的低血糖与高胰岛素血症有关。其发生并未因降低TNF活性或产生而不影响血浆胰岛素水平的治疗而得到预防。相反，它被二氮嗪抑制，二氮嗪抑制胰岛素分泌但不影响TNF产生。此外，在感染伯氏疟原虫期间出现神经症状的小鼠中，当TNF水平高时血糖浓度显著升高，并且在不发生低血糖的非致死性约氏疟原虫感染中，脾脏中的TNF水平在所有感染中最高。给正常动物注射人重组TNF导致血糖水平升高而非下降。转人TNF基因的小鼠在感染约氏疟原虫YM时未发生低血糖，但表现出胰岛素抵抗迹象。根据目前关于TNF在肥胖和葡萄糖稳态控制中的作用的观点，我们得出结论，疟疾的低血糖不是由TNF水平升高引起的，TNF实际上可能是有益的，而是继发于可能由寄生虫产物直接刺激的高胰岛素血症。
