Exogenous interleukin 7 affects gut-associated lymphoid tissue in mice receiving total parenteral nutrition
Exogenous interleukin 7 affects gut-associated lymphoid tissue in mice receiving total parenteral nutrition
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DOI：
10.1097/01.shk.0000183237.32256.78
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发表时间：
2005-12-01
期刊：
影响因子：
3.1
通讯作者：
Hiraide, H
中科院分区：
文献类型：
--
作者：
Fukatsu, K;Moriya, T;Hiraide, H
在缺乏肠内营养输送的情况下，肠道相关淋巴组织（GALT）的质量和功能减少。本研究的目的是研究外源性白细胞介素(IL)-7治疗是否逆转静脉(IV)-全肠外营养（TPN）诱导的GALT、免疫球蛋白（Ig） A水平和肠道屏障功能的变化。89只小鼠随机分为鼠粮、TPN或TPN + IL-7组（1 μ g/kg，每天静脉注射2次），治疗5 d。取整个小肠，从Peyer’s patches （PPs）、上皮内空隙（ie）和固有层（LP）中分离淋巴细胞。测定小肠和支气管肺泡IgA水平。采用酶联免疫吸收法测定小肠近端和远端促iga （IL-10）和抑制iga （IFN - γ）细胞因子水平。灌胃给药1 × 10（10）只铜绿假单胞菌，观察存活情况。与饲料组相比，TPN降低了PPs、IE空间和LP的总细胞产量。IL-7处理恢复细胞数量。TPN + IL-7组PP CD4+、PP CD8+、IE γ δ TCR+、LP CD4+细胞数量均高于TPN组。TPN组和TPN + IL-7组分泌IgA水平低于鼠粮组。在小肠远端，三组的IFN γ水平相似，而TPN和TPN + IL-7组的IL-10水平相对于chow组有所降低。与chow组相比，TPN组的生存时间缩短，但IL-7治疗显著改善了生存。因此，外源性IL-7不会提高分泌IgA水平，也不会对肠道IgA介导细胞因子水平产生显著影响。然而，在TPN期间，IL-7治疗逆转了TPN诱导的GALT萎缩，并提高了肠源性脓毒症模型的生存率。
In the absence of enteral nutrient delivery, gut-associated lymphoid tissue (GALT) mass and function are reduced. The purpose of this study was to examine whether exogenous interleukin (IL)-7 treatment reverses intravenous (IV)-total parenteral nutrition (TPN)-induced changes in GALT, immunoglobulin (Ig) A levels, and gut barrier function. Eighty-nine mice were randomized to chow, TPN, or TPN + IL-7 (1 mu g/kg, administered IV twice a day) and treated for 5 days. The entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (I E) spaces, and the lamina propria (LP). Small intestinal and bronchoalveolar IgA levels were measured. Proximal and distal small intestinal levels of IgA-stimulating (IL-10) and IgA-inhibiting (IFN gamma) cytokines were determined with enzyme-linked immunoabsorbant assay. Moreover, 1 X 10(10) live Pseudomonas aeruginosa were delivered by gavage and survival was observed. TPN decreased total cell yields from PPs, IE spaces, and the LP compared with the chow group. IL-7 treatment restored cell numbers. PP CD4+, PP CD8+, IE gamma delta TCR+, and LP CD4+ cell numbers were higher in the TPN + IL-7 group than in the TPN group. Secretory IgA levels were lower in the TPN and TPN + IL-7 than in the chow group. In the distal small intestine, IFN gamma levels were similar in the three groups, whereas IL-10 levels were reduced in the TPN and TPN + IL-7 groups relative to the chow group. Survival times were reduced in the TPN compared with the chow group, but IL-7 treatment significantly improved survival. Thus, exogenous IL-7 does not improve secretory IgA levels, nor are there any remarkable effects on levels of gut IgA-mediating cytokines. However, IL-7 treatment during TPN reverses TPN-induced GALT atrophy and improves survival in a gut-derived sepsis model.