Koff W C, Dunegan M A
J Immunol. 1985 Jul;135(1):350-4.
Recent evidence has suggested that stress may suppress the immune system and increase the frequency and severity of viral and neoplastic disease. The mechanisms for stress-induced modulation of immune function are unclear, but several neuropeptides are thought to be involved. Because macrophages play an important role in the host defense against infection and neoplasia, several stress-related neuropeptides were screened in efforts to determine whether these substances affect macrophage-mediated tumoricidal activity. Adrenocorticotropin and noradrenaline each completely blocked the capacity of mouse recombinant interferon-gamma (INF-gamma) to activate murine peritoneal macrophages to a tumoricidal state as measured by the lysis of 125I-UdR-labeled melanoma target cells. Vasoactive intestinal peptide significantly potentiated the suppressive effects of noradrenaline. In contrast, neurotensin markedly enhanced the cytolytic capability of peritoneal macrophages activated with INF-gamma. Several other neuropeptides, including substance P, alpha-endorphin, beta-endorphin, Leu-enkephalin, and Met-enkephalin, had no effect on macrophage activation. These findings demonstrate that selected stress-related neuropeptides and neurohormones significantly modulate the capacity of macrophages to attain a tumoricidal state and suggest that alteration of macrophage function by neuropeptides may be a prominent feature of stress-induced enhancement of neoplastic disease.
最近有证据表明，压力可能会抑制免疫系统，并增加病毒和肿瘤疾病的发生频率及严重程度。压力诱导免疫功能调节的机制尚不清楚，但有几种神经肽被认为与之有关。由于巨噬细胞在宿主抵御感染和肿瘤形成中发挥着重要作用，因此对几种与压力相关的神经肽进行了筛选，以确定这些物质是否会影响巨噬细胞介导的杀肿瘤活性。促肾上腺皮质激素和去甲肾上腺素均完全阻断了小鼠重组干扰素-γ（INF-γ）将小鼠腹腔巨噬细胞激活至杀肿瘤状态的能力，这一能力通过125I-UdR标记的黑色素瘤靶细胞的裂解来测定。血管活性肠肽显著增强了去甲肾上腺素的抑制作用。相比之下，神经降压素显著增强了经INF-γ激活的腹腔巨噬细胞的溶细胞能力。其他几种神经肽，包括P物质、α-内啡肽、β-内啡肽、亮氨酸脑啡肽和甲硫氨酸脑啡肽，对巨噬细胞激活没有影响。这些发现表明，特定的与压力相关的神经肽和神经激素可显著调节巨噬细胞达到杀肿瘤状态的能力，并提示神经肽对巨噬细胞功能的改变可能是压力诱导肿瘤疾病加重的一个突出特征。
