INVITRO PRODUCTION OF IL-1-BETA, IL-1-ALPHA, TNF AND IL-2 IN HEALTHY-SUBJECTS - DISTRIBUTION, EFFECT OF CYCLOOXYGENASE INHIBITION AND EVIDENCE OF INDEPENDENT GENE-REGULATION
INVITRO PRODUCTION OF IL-1-BETA, IL-1-ALPHA, TNF AND IL-2 IN HEALTHY-SUBJECTS - DISTRIBUTION, EFFECT OF CYCLOOXYGENASE INHIBITION AND EVIDENCE OF INDEPENDENT GENE-REGULATION
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DOI：
10.1002/eji.1830191222
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发表时间：
1989-12-01
影响因子：
5.4
通讯作者：
DINARELLO, CA
中科院分区：
文献类型：
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作者：
ENDRES, S;CANNON, JG;DINARELLO, CA
许多研究已经报道了在各种疾病中体内细胞因子的产生发生改变。在本研究中，我们使用特异性免疫分析法来定量IL-1β的产生。(IL-1β)、IL-1α、肿瘤坏死因子(TNF)和IL-2。本文研究了21例正常人外周血单核细胞(PBMC)中细胞相关和分泌细胞因子的分布；细胞相关IL-1β在脂多糖(LPS)作用下的比例。IL-1α为13%~56%。29%~98%，肿瘤坏死因子2%~17%。在一个由32名受试者组成的大队列中，对脂多糖或植物血凝素的反应产生的免疫反应细胞因子的总量通常分布在研究组内。平均产生IL-1α。对内毒素的反应为10.1 ng/ml，并超过IL-1β的产生。(5.6 ng/ml)和(2.2 ng/ml)。这种分布模式的特点是学科间的高度可变性，跨越两个数量级，存在高和低的“生产者”。白介素1.α的产生。和IL-1β。相关系数R=0.69。相反，IL-1β的产生。与肿瘤坏死因子和白介素2的产生无相关性。在PBMC刺激过程中加入吲哚美辛可增加IL-1β的含量。与不加消炎痛的培养相比，显示出较高的相关性(R=0.83)。因此，IL-1β产量低。在某些受试者中，似乎不是由于环氧合酶产物的可抑制水平。在一项回顾性研究中，12名服用环氧合酶抑制剂的受试者的PBMC产生的IL-1β增加了43%。比没有服用这些药物的受试者多(p<；0.05)。这些研究表明，PBMC合成的细胞因子的数量(A)与IL-1、TNF和IL-2独立调节；(B)与IL-1β相关。和IL 1α；(C)对于低和高“生产者”是固有的，和(D)IL 1β的产生随着口服环氧合酶抑制剂的使用而增加。
Numerous studies have reported altered in vivo cytokine production in various diseases. In the present study we used specific immunoassays to quantitate production of interleukin 1.beta. (IL 1.beta.), IL 1.alpha., tumor necrosis factor (TNF) and IL2 from human peripheral blood mononuclear cells (PBMC). The distribution of cell-associated and secreted cytokines was studied in PBMC of 21 individuals; in response to lipopolysaccharide (LPS) the proportion of cell-associated IL 1.beta. ranged from 13% to 56%, for IL 1.alpha. 29% to 98%, and for TNF 2% to 17%. In a large cohort of 32 subjects, the total amount of immunoreactive cytokines produced in response to LPS or phytohemagglutin was normally distributed within the study group. Mean production of IL 1.alpha. in response to LPS was 10.1 ng/ml and exceeded production of iL 1.beta. (5.6 ng/ml)and TNF (2.2 ng/ml). The distribution pattern was characterized by high intersubject variability extending over two orders of magnitude and the presence of high and low "producers". Production of IL1 .alpha. and IL 1.beta. correlated (R = 0.69). In contrast, production of IL 1.beta. did not correlate with production of TNF or IL2. Indomethacin present during stimulation of PBMC increased the amount of IL 1.beta. produced and showed a high correlation (R = 0.83) compared to cultures without indomethacin. Thus, low production of IL 1.beta. in certain subjects appears not to be due to inhibitable levels of cyclooxygenase products. In a retrospective study, PBMC from 12 subjects who had taken oral cyclooxygenase inhibitors during the preceding 7 days produced 43% more IL 1.beta. than subjects who did not take these drugs (p < 0.05). These studies demonstrate that the amount of cytokine synthesized by PBMC (a) is regulated independently for IL 1, TNF and IL 2; (b) correlates for IL 1.beta. and IL 1.alpha.; (c) is intrinsic for low and high "producers", and (d) production of IL 1.beta.increases with the use of oral cyclooxygenase inhibitors.