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人体热损伤后的自体和异体混合淋巴细胞反应:白细胞介素1、白细胞介素2和一种前列腺素抑制剂WY-18251的免疫调节作用。

Autologous and allogeneic mixed-lymphocyte responses following thermal injury in man: the immunomodulatory effects of interleukin 1, interleukin 2, and a prostaglandin inhibitor, WY-18251.

作者信息

Antonacci A C, Calvano S E, Reaves L E, Prajapati A, Bockman R, Welte K, Mertelsmann R, Gupta S, Good R A, Shires G T

出版信息

Clin Immunol Immunopathol. 1984 Feb;30(2):304-20. doi: 10.1016/0090-1229(84)90064-3.

DOI:10.1016/0090-1229(84)90064-3
PMID:6229378
Abstract

A group of 30 burn patients with 36-87% total body surface area (TBSA) burns was studied at 24-48 hr postburn. These included studies of (1) autologous and allogeneic mixed-lymphocyte reactions (MLR); (2) the immunoregulatory influence of mitomycin C-treated T cells, non-T cells, and unfractionated peripheral blood lymphocytes (PBL) on allogeneic MLR; and (3) correlation between the proportions of T-cell subsets defined with monoclonal antibodies (OKT4 and OKT8) and autologous MLR. Studies concerning adherent cell production of thromboxane, prostaglandin E2, and prostaglandin F2a and the immunomodulatory effects of Interleukin 1 (IL-1), Interleukin 2 (IL-2), and a prostaglandin inhibitor, WY-18251, on autologous MLR are presented. The autologous mixed-lymphocyte reaction was depressed in 60% of the burn patients tested. This depressed response correlated closely to the extent of third-degree injury (P less than 0.025) and to TBSA injury greater than 60% (P less than 0.025). A linear correlation was observed between the depression in autologous MLR and a decrease in both the percentage of OKT4+ T cells and the OKT4+/OKT8+ ratio. The response of T cells from burn patients in allogeneic MLR was normal. Age, sex, TBSA of the burn, and size of second-degree burn did not correlate with the abnormalities observed in MLR. Mitomycin C-treated mononuclear cells, purified T cells, or non-T cells from burned patients did not demonstrate any suppressive influence on MLR in normals. Monocyte number and arachidonic acid metabolism were investigated. In addition to increased numbers of monocytes following thermal injury, adherent cells produced increased quantities of thromboxane, prostaglandin E2, and prostaglandin F2a. The effects of Interleukin 1, Interleukin 2, and a prostaglandin inhibitor, WY-18251, were studied in autologous MLR (AMLR) of burned and normal patients. Interleukin 1 and WY-18251 did not induce any significant changes in proliferation in burned patients or normal controls. When compared to cultures without exogenous IL-2, an increase in AMLR was observed following the addition of IL-2 to burn patient cultures at Day 6 and Day 7 of culture. Although the addition of IL-2 did increase proliferation in AMLR of normal controls at Day 6 and Day 7, the enhancement observed for the burn patient cultures represented a restoration to the level of normal control cultures without IL-2. A dose-dependent increase in AMLR was observed in T cells isolated from normal and burned patients in the presence of purified Interleukin 2.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

对一组30名烧伤患者进行了研究,这些患者的烧伤面积占总体表面积(TBSA)的36%-87%,研究时间为烧伤后24-48小时。研究内容包括:(1)自体和异体混合淋巴细胞反应(MLR);(2)丝裂霉素C处理的T细胞、非T细胞和未分离的外周血淋巴细胞(PBL)对异体MLR的免疫调节作用;(3)用单克隆抗体(OKT4和OKT8)定义的T细胞亚群比例与自体MLR之间的相关性。还介绍了关于贴壁细胞产生血栓素、前列腺素E2和前列腺素F2α的研究,以及白细胞介素1(IL-1)、白细胞介素2(IL-2)和一种前列腺素抑制剂WY-18251对自体MLR的免疫调节作用。在接受测试的烧伤患者中,60%的患者自体混合淋巴细胞反应受到抑制。这种反应抑制与三度烧伤的程度密切相关(P<0.025),也与TBSA损伤大于60%密切相关(P<0.025)。观察到自体MLR的抑制与OKT4+T细胞百分比和OKT4+/OKT8+比值的降低之间存在线性相关性。烧伤患者T细胞在异体MLR中的反应正常。年龄、性别、烧伤的TBSA和二度烧伤的面积与MLR中观察到的异常情况无关。来自烧伤患者的经丝裂霉素C处理的单核细胞、纯化的T细胞或非T细胞对正常人的MLR没有显示出任何抑制作用。对单核细胞数量和花生四烯酸代谢进行了研究。除了热损伤后单核细胞数量增加外,贴壁细胞产生的血栓素、前列腺素E2和前列腺素F2α的量也增加。研究了白细胞介素1、白细胞介素2和一种前列腺素抑制剂WY-18251对烧伤患者和正常患者自体MLR(AMLR)的影响。白细胞介素1和WY-18251在烧伤患者或正常对照中均未诱导增殖的任何显著变化。与未添加外源性IL-2的培养物相比,在培养的第6天和第7天向烧伤患者培养物中添加IL-2后,观察到AMLR增加。虽然在第6天和第7天添加IL-2确实增加了正常对照AMLR中的增殖,但烧伤患者培养物中观察到的增强代表恢复到未添加IL-2的正常对照培养物的水平。在存在纯化的白细胞介素2的情况下,从正常和烧伤患者分离的T细胞中观察到AMLR呈剂量依赖性增加。(摘要截短至400字)

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