Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection.
Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection.
复制标题
严重损伤会导致 T 辅助细胞 2 淋巴细胞表型占主导地位，并导致白细胞介素 12 产生减少，从而导致抗感染能力下降。
DOI：
10.1097/00000658-199522240-00006
复制
发表时间：
1995
影响因子：
9
通讯作者：
Rodrick,ML
中科院分区：
文献类型：
--
作者：
O'Sullivan,ST;Lederer,JA;Horgan,AF;Chin,DH;Mannick,JA;Rodrick,ML
目的：研究了严重创伤性损伤和大面积烧伤的患者以及烧伤的动物模型，以确定损伤对T辅助细胞-2淋巴细胞表型典型的细胞因子（与T辅助细胞-1表型相对）的产生以及对白细胞介素-12的产生的影响。自然免疫和过继免疫的紊乱与严重受伤和烧伤患者对感染的易感性增加有关。早期的研究表明，损伤后的过继性免疫受损的特征是Th淋巴细胞的产物白细胞介素-2（IL-2）的产生减少。初始Th细胞暴露于某些抗原和细胞因子导致转化为Th-1或Th-2表型。Th-1细胞产生IL-2和干扰素-γ（IFN-[tau]）并启动细胞免疫。Th-2细胞分泌白细胞介素-4（IL-4）和白细胞介素-10（IL-10）并刺激某些抗体的产生。IL-12促进向Th-1表型的转化，IL-4促进向Th-2表型的转化。作者认为，严重的损伤可能会导致Th细胞的Th-2，而不是Th-1表型，而不是广义的Th suppress.Methods：作者研究了循环外周血单个核细胞（PBMC）从16个主要烧伤和8创伤患者32次受伤后早期和13个年龄和性别匹配的健康人的细胞因子产生后植物血凝素刺激。还研究了一种20%烧伤的小鼠模型，该模型已知模拟了烧伤患者中观察到的免疫异常。用刀豆球蛋白A或金黄色葡萄球菌科万菌株I激活烧伤小鼠脾细胞（每组10 ~ 12只）后，通过逆转录聚合酶链反应测定细胞因子产生和细胞因子信使RNA表达。将烧伤小鼠与假烧伤对照组进行比较，并将注意力集中在烧伤后第10天，此时IL-2的产生和对感染的抵抗力受到高度抑制。最后，烧伤和假烧伤动物，每组20只，用IL-12在体内治疗（每天25 ng，持续5天），并观察脓毒症攻毒后的死亡率受伤后第10天进行（盲肠结扎和穿孔[CLP]）。结果：来自烧伤和创伤患者的外周血单核细胞产生较少的IFN-[tau]，即Th-1细胞的指标细胞因子，与烧伤后1至14天来自健康个体的PBMC相比（SE= 77.6+/-16 pg/mL患者对141.3+/-35 pg/mL对照，p< 0.05）。然而，患者PBMC产生的IL-4（Th-2细胞的指标细胞因子）增加（患者51.0+/-13.0 pg/mL对对照26.9+/-2.5 pg/mL，p< 0.05）。与假烧伤对照相比，烧伤后10天小鼠的脾细胞显示IL-2（1.04+/-0.91单位/mL烧伤vs. 5.8+/-0.55单位/mL对照，p< 0.05）和IFN-[tau]（1.05+/-0.7单位/mL烧伤vs. 12.0+/-8.9单位/mL对照，p< 0.05）的产生减少。然而，烧伤脾细胞产生更多的IL-4（2492+/-157.0 pg/mL烧伤vs. 672.0+/-22.7 pg/mL对照，p< 0.01）和IL-10（695.2+/-20.8 pg/mL烧伤vs. 567.0+/-16.7 pg/mL对照，p< 0.05）。与假烧伤（0.46+/-0.08单位/mL，p< 0.05）相比，烧伤后脾细胞产生IL-12（0.20+/-0.035单位/mL）也减少。烧伤脾细胞产生的IL-2、IFN-[tau]和IL-12的减少反映在它们各自的细胞因子mRNA表达的十倍减少。烧伤动物的体内IL-12治疗使损伤后第10天CLP的死亡率从85%降低至15%（CLP后假烧伤死亡率，15%，p<0.05）。
Objective: Patients with serious traumatic injury and major burns and an animal model of burn injury were studied to determine the effect of injury on the production of cytokines typical of the T helper-2 lymphocyte phenotype as opposed to the T helper-1 phenotype and on the production of interleukin-12.Summary Background Data: Perturbations of natural and adoptive immunity are related to the increased susceptibility to infection manifested by seriously injured and burn patients. Earlier work has shown that impaired adoptive immunity after injury is characterized by diminished production of interleukin-2 (IL-2), a product of Th lymphocytes. Exposure of naive Th cells to certain antigens and cytokines causes conversion to either the Th-1 or the Th-2 phenotype. Th-1 cells produce IL-2 and interferon-gamma (IFN-[tau]) and initiate cellular immunity. Th-2 cells secrete interleukin-4 (IL-4) and interleukin-10 (IL-10) and stimulate production of certain antibodies. Conversion to the Th-1 phenotype is facilitated by IL-12, and conversion to the Th-2 phenotype is promoted by IL-4. The authors believed that serious injury might cause conversion of Th cells to the Th-2 as opposed to the Th-1 phenotype rather than generalized Th suppression.Methods: The authors studied circulating peripheral blood mononuclear cells (PBMC) from 16 major burn and 8 trauma patients on 32 occasions early after injury and from 13 age-and sex-matched healthy individuals for cytokine production after phytohemagglutinin stimulation. Also studied was a mouse model of 20% burn injury known to mimic the immune abnormalities seen in humans with burns. Splenocytes from burn mice, 10 to 12 per group, were studied after activation by concanavalin A or by the bacterial antigen Staphylococcus aureus Cowan strain I for cytokine production and cytokine messenger RNA expression as determined by reverse transcriptase polymerase chain reaction. Burn mice were compared with sham-burn controls and attention was focused on day 10 after burn injury, a time when IL-2 production and resistance to infection are highly suppressed. Finally, burn and sham-burn animals, 20 per group, were treated in vivo with IL-12 (25 ng daily for 5 days) and observed for mortality after septic challenge (cecal ligation and puncture [CLP]) performed on day 10 after injury.Results: Peripheral blood mononuclear cells from burn and trauma patients produced less IFN-[tau], the index cytokine of Th-1 cells, than PBMCs from healthy individuals 1 to 14 days after burn injury (SE= 77.6+/-16 pg/mL patients vs. 141.3+/-35 pg/mL controls, p< 0.05). However, production of IL-4, the index cytokine of Th-2 cells, by patient PBMCs was increased (51.0+/-13.0 pg/mL patients vs. 26.9+/-2.5 controls, p< 0.05). Splenocytes from mice 10 days after burn injury, when compared with sham-burn controls, showed diminished production of IL-2 (1.04+/-0.91 units/mL burns vs. 5.8+/-0.55 units/mL controls, p< 0.05) and IFN-[tau](1.05+/-0.7 units/mL burns vs. 12.0+/-8.9 units/mL controls, p< 0.05). However, burn splenocytes produced more IL-4 (2492+/-157.0 pg/mL burns vs. 672.0+/-22.7 pg/mL controls, p< 0.01) and IL-10 (695.2+/-20.8 pg/mL burns vs. 567.0+/-16.7 pg/mL controls, p< 0.05). Splenocyte production of IL-12 was also reduced after burn (0.20+/-0.035 units/mL) as compared with sham burn (0.46+/-0.08 units/mL, p< 0.05). The reduction in IL-2, IFN-[tau], and IL-12 production by burn splenocytes was reflected by a tenfold decrease in expression of their respective cytokine mRNAs. In vivo IL-12 treatment of burn animals decreased mortality from CLP on day 10 after injury from 85% to 15%(sham-burn mortality after CLP, 15%, p< …