Margatho Rafael O, Massoco Cristina de O, Calefi Atilio S, Cruz Daniel S G, Sandini Thaisa M, Alves Glaucie Jussilane, Florio Jorge C, Palermo-Neto João
Neuroimmunomodulation Research Group, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
Neuroimmunomodulation. 2017;24(1):40-53. doi: 10.1159/000477938. Epub 2017 Aug 9.
Cohabitation with Ehrlich tumor-bearing (ETB) mice induced behavioral, neurochemical, hormonal, and immune effects in the conspecifics as a consequence of stress-induced activation of the sympathetic nervous system (SNS) with catecholamine release. In the current study, the nonspecific β-AR blocker d,l-propranolol and the specific β2-AR blocker ICI-118.551 were employed as pharmacological tools to assess the extent to which catecholamines participated in the effects induced by cohabitation with ETB mice.
Two experiments were performed, 1 with d,l-propranolol treatment and the other with ICI-118.551. One mouse in the experimental group was called the "companion of the sick partner" (CSP) since it was forced to live in the same cage with 2 (experiment 1) or 1 (experiment 2) cage mate that had been i.p. injected with 5 × 106 Ehrlich tumor cells.
The d,l-propranolol treatment, but not the ICI-118.551 treatment, attenuated the effects of cohabitation with 2 ETB mice on both open-field behavior and the hypothalamic levels and turnover rate of norepinephrine. The 2 β-AR blockers were unable to change the serum corticosterone levels and adrenal weights of the CSP mice; however, these drugs abrogated the effects of cohabitation on neutrophil oxidative burst and phagocytosis. Finally, an increase in the 5-HT turnover rate was observed in the olfactory bulb of CSP mice compared to their respective controls, an effect that was not modified by β-AR blockade.
These results confirm and strengthen our hypothesis that the SNS is involved in the effects induced by cohabitation with ETB mice and point towards β2-AR participation in the immune effects analyzed.
与荷艾氏瘤小鼠（ETB）同居会因应激诱导的交感神经系统（SNS）激活及儿茶酚胺释放，对同种小鼠产生行为、神经化学、激素和免疫方面的影响。在本研究中，非特异性β-肾上腺素能受体（β-AR）阻滞剂d，l-普萘洛尔和特异性β2-AR阻滞剂ICI-118.551被用作药理学工具，以评估儿茶酚胺在与ETB小鼠同居诱导的效应中所起作用的程度。
进行了两项实验，一项用d，l-普萘洛尔治疗，另一项用ICI-118.551治疗。实验组中的一只小鼠被称为“患病伙伴的同伴”（CSP），因为它被迫与2只（实验1）或1只（实验2）经腹腔注射5×10⁶个艾氏瘤细胞的同笼伙伴生活在同一笼子里。
d，l-普萘洛尔治疗可减轻与2只ETB小鼠同居对旷场行为以及下丘脑去甲肾上腺素水平和周转率的影响，但ICI-118.551治疗无此效果。两种β-AR阻滞剂均无法改变CSP小鼠的血清皮质酮水平和肾上腺重量；然而，这些药物消除了同居对中性粒细胞氧化爆发和吞噬作用的影响。最后，与各自的对照组相比，CSP小鼠嗅球中的5-羟色胺周转率增加，β-AR阻断未改变这一效应。
这些结果证实并强化了我们的假设，即SNS参与了与ETB小鼠同居诱导的效应，并表明β2-AR参与了所分析的免疫效应。
