Metabolic-cytokine responses to a second immunological challenge with LPS in mice with T-gondii infection
Metabolic-cytokine responses to a second immunological challenge with LPS in mice with T-gondii infection
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DOI：
10.1152/ajpendo.1998.274.3.e439
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发表时间：
1998-03-01
影响因子：
5.1
通讯作者：
Dulloo, AG
中科院分区：
文献类型：
--
作者：
Arsenijevic, D;Girardier, L;Dulloo, AG
将10个弓形虫包囊（Me 49株）注射到瑞士韦伯斯特小鼠中，导致1）持续2-3周的急性感染期，其特征为体重减轻，和2）慢性期，其中存活小鼠显示部分体重恢复（Gainer）或持续但稳定的恶病质（Nonginer）。在感染的慢性期对脂多糖（LPS）的第二次免疫刺激的反应中，显示了1）两组感染小鼠的能量消耗的增加比对照组更长，2）摄食不足的强度和持续时间也受到不同的影响，其中Nonginer> Gainer>对照，感染组小鼠血清肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-10水平高于对照组，IL-10/TNF-α比值低于对照组。相反，血清IL-4在所有三组中升高至相同水平。通过静脉注射伊文思蓝对血脑屏障通透性的评估显示，仅感染的非感染者的脑中有明显的染色。总之，这些结果表明，在慢性弓形虫病小鼠中，第二次非特异性攻击（LPS）加剧了低吞噬和高代谢状态，后者与TNF-α和IL-10产生的高反应性相关。此外，表现出持续性恶病质的小鼠中的摄食不足状态的更大恶化可能是由于血脑屏障的预先存在的更高渗透性，这将允许血浆携带的细胞因子和/或其他神经免疫活性物质更大程度地进入中枢神经系统。
Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss Webster mice results in 1) an acute phase of infection lasting for 2-3 wk, characterized by weight loss, and 2) a chronic phase in which surviving mice show either partial weight recovery (Gainers) or persistent, although stable, cachexia (Nongainers). In response to a second immunological stimulation with lipopolysaccharide (LPS) in the chronic phase of the infection, it is shown that 1) the increase in energy expenditure was more prolonged in both groups of infected mice than in controls, 2) the intensity and duration of hypophagia were also differently affected with Nongainers > Gainers > controls, and 3) the infected mice had higher serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-10 and a lower ratio of IL-10 to TNF-alpha than controls. In contrast, serum IL-4 increased to the same level in all three groups. Evaluation of the permeability of the blood-brain barrier by intravenous injection of Evans blue revealed a marked staining in the brain of only the infected Nongainers. Taken together, these results indicate that, in mice with chronic toxoplasmosis, a second nonspecific challenge (with LPS) exacerbates the hypophagic and hypermetabolic states, the latter being associated with hyperresponsiveness in TNF-alpha and IL-10 production. Furthermore, the greater exacerbation of the hypophagic state in mice showing persistent cachexia may be due to a preexisting higher permeability of the blood-brain barrier, which would allow a greater access of plasma-borne cytokines and/or other neuroimmunologically active substances to the central nervous system.