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人白细胞提取物经口服、皮下和腹腔注射途径给药后对感染小鼠全身免疫反应和囊肿生长的差异活性。

Differential Activity of Human Leukocyte Extract on Systemic Immune Response and Cyst Growth in Mice with Infection After Oral, Subcutaneous and Intraperitoneal Routes of Administration.

作者信息

Ciglanová D, Jurčacková Z, Mudroňová D, Dvorožňáková E, Hrčková G

机构信息

Institute of Parasitological, Slovak Academy of Sciences, Experimental Pharmacology, Hlinkova 3, 04001 Košice, Slovak Republic.

University of Veterinary Medicine and Pharmacy in Košice, Komenského 58, 041 81 Košice, Slovak Republic.

出版信息

Helminthologia. 2022 Dec 30;59(4):341-356. doi: 10.2478/helm-2022-0038. eCollection 2022 Dec.

DOI:10.2478/helm-2022-0038
PMID:36875680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9979067/
Abstract

Alveolar echinococcosis (AE) caused by the larval stage of is serious parasitic diseases associated with the host´s immunosuppression. The effects of human non-immune dialyzable leukocyte extract (DLE) on immune cells in blood and spleen and parasitic cysts weight in Balb/c mice after oral (PO), subcutaneous (SC) and intraperitoneal administration (IP) were compared. The reduction in cysts weight (p < 0.01) was recorded after PO route, whereas moderate reduction was found after SC and IP routes. The elevation of lymphoid populations in blood and spleen was found after PO administration (p < 0.01) in parallel with reduced myeloid population. Infection-elicited decline in B220+B cells was partially abolished by PO route, but DLE routes did not influence the CD3+ T cells. The proportions of CD3+CD4+Th lymphocytes were moderately upregulated, whereas CD3+CD8+Tc populations were reduced after all DLE routes (p < 0.01). PO administration increased CD11b+MHCII blood monocytes, CD11b-SigleF+ cell, but not CD11b+Si-glecF+ eosinophils in the blood, stimulated after SC and IP routes. DLE induced downregulation of NO production by LPS-stimulated adherent splenocytes . Con A-triggered T lymphocyte proliferation was associated with the elevated IFN-γ production and transcription factor Tbet mRNA expression. The alleviation of Th2 (IL-4) and Treg (TGF-β) cytokine production by lymphocytes paralleled with downregulation of gene transcription for cytokines, GATA and FoxP3. Reduction of myeloid cells with suppressive activity was found. The SC and IP routes affected partially the cysts weights, diminished significantly gene transcription, NO levels and Th2 and Treg cytokines production. Results showed that PO route of DLE administration was the most effective in ameliorating immunosuppression via stimulation of Th1 type, reducing Th2 and Treg type of immunity and CD3+CD8+Tc lymphocytes in the blood and spleens during infection in mice.

摘要

由细粒棘球绦虫幼虫阶段引起的肺泡型棘球蚴病(AE)是一种与宿主免疫抑制相关的严重寄生虫病。比较了人非免疫性可透析白细胞提取物(DLE)经口服(PO)、皮下(SC)和腹腔注射(IP)给药后对Balb/c小鼠血液和脾脏中免疫细胞以及寄生虫囊肿重量的影响。口服给药后囊肿重量减轻(p < 0.01),而皮下和腹腔注射途径后发现有中度减轻。口服给药后血液和脾脏中淋巴细胞群体增加(p < 0.01),同时髓细胞群体减少。口服途径部分消除了感染引起的B220+B细胞减少,但DLE给药途径对CD3+T细胞没有影响。所有DLE给药途径后,CD3+CD4+Th淋巴细胞比例适度上调,而CD3+CD8+Tc群体减少(p < 0.01)。口服给药增加了血液中CD11b+MHCII血单核细胞、CD11b-SigleF+细胞,但不增加CD11b+Si-glecF+嗜酸性粒细胞,皮下和腹腔注射途径后有刺激作用。DLE诱导LPS刺激的贴壁脾细胞产生的NO下调。伴刀豆球蛋白A触发的T淋巴细胞增殖与IFN-γ产生增加和转录因子Tbet mRNA表达相关。淋巴细胞产生的Th2(IL-4)和Treg(TGF-β)细胞因子的减轻与细胞因子、GATA和FoxP3基因转录的下调平行。发现具有抑制活性的髓细胞减少。皮下和腹腔注射途径部分影响囊肿重量,显著降低基因转录、NO水平以及Th2和Treg细胞因子的产生。结果表明,在小鼠感染期间,口服DLE给药途径通过刺激Th1型、降低Th2和Treg型免疫以及血液和脾脏中CD3+CD8+Tc淋巴细胞,在改善免疫抑制方面最有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9cc/9979067/fb06f85da544/helm-59-341-g010.jpg
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