Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
Brain Behav Immun. 2010 Feb;24(2):281-8. doi: 10.1016/j.bbi.2009.10.007. Epub 2009 Oct 29.
Mouse-adapted human influenza virus is detectable in the olfactory bulbs of mice within hours after intranasal challenge and is associated with enhanced local cytokine mRNA and protein levels. To determine whether signals from the olfactory nerve influence the unfolding of the acute phase response (APR), we surgically transected the olfactory nerve in mice prior to influenza infection. We then compared the responses of olfactory-nerve-transected (ONT) mice to those recorded in sham-operated control mice using measurements of body temperature, food intake, body weight, locomotor activity and immunohistochemistry for cytokines and the viral antigen, H1N1. ONT did not change baseline body temperature (Tb); however, the onset of virus-induced hypothermia was delayed for about 13 h in the ONT mice. Locomotor activity, food intake and body weights of the two groups were similar. At 15 h post-challenge fewer viral antigen-immunoreactive (IR) cells were observed in the olfactory bulb (OB) of ONT mice compared to sham controls. The number of tumor necrosis factor alpha (TNFalpha)- and interleukin 1beta (IL1beta)-IR cells in ONT mice was also reduced in the OB and other interconnected regions in the brain compared to sham controls. These results suggest that the olfactory nerve pathway is important for the initial pathogenesis of the influenza-induced APR.
鼻腔感染流感病毒后数小时，小鼠嗅球中即可检测到适应小鼠的人源流感病毒，并且与局部细胞因子 mRNA 和蛋白水平升高相关。为了确定嗅神经信号是否影响急性期反应（APR）的发生，我们在流感感染前对小鼠进行嗅神经横断术。然后，我们通过测量体温、摄食量、体重、运动活性和细胞因子及病毒抗原 H1N1 的免疫组化，比较嗅神经切断（ONT）小鼠和假手术对照小鼠的反应。ONT 不改变基础体温（Tb）；然而，ONT 小鼠中病毒引起的体温过低的发作延迟了约 13 小时。两组的运动活性、摄食量和体重相似。在感染后 15 小时，ONT 小鼠嗅球（OB）中观察到的流感病毒抗原免疫反应（IR）细胞较少，与假对照相比。ONT 小鼠的肿瘤坏死因子 alpha（TNFalpha）和白细胞介素 1beta（IL1beta）-IR 细胞数量在 OB 和大脑中其他相互连接的区域也减少。这些结果表明，嗅神经通路对流感诱导的 APR 的初始发病机制很重要。
