Shmarina G V, Pukhalsky A L, Kokarovtseva S N, Pukhalskaya D A, Shabalova L A, Kapranov N I, Kashirskaja N J
Laboratory of Immunogenetics, Research Centre for Medical Genetics, Moscow, Russia.
Mediators Inflamm. 2001 Aug;10(4):191-7. doi: 10.1080/09629350123387.
The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-alpha contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators.
In the present study, the relationships between TNF-alpha and IL-10 in the plasma of healthy school-children and cystic fibrosis (CF) patients have been investigated.
Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits.
Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF-alpha/IL-10 > 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-alpha or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed.
There were no fundamental differences between CF and healthy children in the regulation of TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-alpha, whereas immune disturbance was characterized by IL-10 superiority. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli.
肿瘤坏死因子-α（TNF-α）与白细胞介素-10（IL-10）之间的平衡对于维持免疫稳态至关重要。TNF-α的过度产生会导致过度的炎症反应和组织损伤。但是，通常情况下，TNF-α的增加会被抗炎细胞因子IL-10的同时合成所抵消，IL-10会抑制许多激活和调节介质的产生。
在本研究中，对健康学童和囊性纤维化（CF）患者血浆中TNF-α与IL-10之间的关系进行了研究。
从12例患有慢性肺病的CF患者和接种减毒活风疹疫苗的18名健康学童中采集血样。使用市售的酶联免疫吸附测定试剂盒测定血浆样本中的IL-10和TNF-α。
接种疫苗前，大多数健康儿童（18名中的13名）表现出促炎因子TNF-α优于抗炎因子IL-10（TNF-α/IL-10>1）。在这些受试者中，发现细胞因子值之间存在显著的正线性关联。疫苗激发导致TNF-α/IL-10比值显著降低。此外，观察到细胞因子值之间的相关性消失。这种紊乱与接种后IL-10水平的过度升高有关。相反，在CF患者中，血浆细胞因子值保持强烈的线性关联，与TNF-α或IL-10的优势无关。在6个月的观察期内，未发现CF患者血浆中IL-10水平有峰值。
CF患者和健康儿童在TNF-α和IL-10分泌调节方面没有根本差异。因此，免疫静止似乎与TNF-α的优势有关，而免疫紊乱的特征是IL-10占优。在CF患者中发现的唯一异常是他们无法对抗原刺激无限产生IL-10。
