Synergistic effects of interleukin 4 and interferon-gamma on monocyte phosphodiesterase activity.
Synergistic effects of interleukin 4 and interferon-gamma on monocyte phosphodiesterase activity.
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白介素 4 和干扰素 γ 对单核细胞磷酸二酯酶活性的协同作用。
DOI：
10.1111/1523-1747.ep12611858
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Hanifin,JM
中科院分区：
文献类型：
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作者：
Li,SH;Chan,SC;Toshitani,A;Leung,DY;Hanifin,JM
与正常（NL）受试者相比，特应性皮炎（AD）患者白细胞环腺苷酸磷酸二酯酶（PDE）活性升高，体外IgE合成增加。白细胞介素4（IL-4）、干扰素-γ（IFN-γ）和PDE抑制剂已显示调节体外IgE合成。本研究调查了可溶性T细胞因子如IL-4和IFN-γ是否可以解释AD患者PDE活性升高。rhIL-4和IFN-γ均显著增加正常单核细胞PDE活性，最高分别为对照组的188%（n = 6，p < 0.05）和315%（n = 3，p < 0.05）。在低于0.1单位/ml的浓度下，IL-4和IFN-γ对单核细胞PDE的活化具有协同作用。AD和NL T细胞培养上清液也显著刺激正常单核细胞PDE活性，但AD T细胞培养上清液中的刺激活性并不显著更大。细胞因子和T细胞上清液对正常单核细胞的作用分别被抗IL-4和IFN-γ的抗体抑制。本研究表明，IL-4和IFN-γ可以增加正常单核细胞中PDE的活性。尽管用酶联免疫吸附测定（ELISA）测定法无法检测到T细胞上清液中的IL-4和IFN-γ水平，但低于可检测水平的这些细胞因子的浓度可以以协同和剂量依赖性方式显著增加单核细胞的PDE活性。这些结果表明，奎宁介导的单核细胞活化可以增加PDE活性。此外，淋巴因子可能在调节环核苷酸调节途径中发挥重要作用。
Patients with atopic dermatitis (AD) have elevated leukocyte cyclic AMP-phosphodiesterase (PDE) activity and increased in vitro IgE synthesis compared to normal (NL) subjects. Interleukin 4 (IL-4) interferon-gamma (IFN-γ), and PDE inhibitor have been shown to regulate in vitro IgE synthesis. This study investigated whether soluble T-cell factors such as IL-4 and IFN-γ could account for elevated PDE activity in patients with AD. Both rhIL-4 and IFN-γ significantly increased normal monocyte PDE activity to a maximum of 188% (n = 6, p < 0.05) and 315% above control (n = 3, p < 0.05), respectively. At concentrations below 0.1 units/ml IL-4 and IFN-γ had Synergistic effects on activation of monocyte PDE. AD and NL T-cell culture supernatants also significantly stimulated normal monocyte PDE activity, but the stimulatory activity was not significantly greater in the AD T-cell supernatants. The effect of both cytokines and T-cell supernatants on normal monocytes was inhibited by antibodies against IL-4 and IFN-γ, respectively. This study demonstrates that IL-4 and IFN-γ can increase PDE activity in normal monocytes. Though the levels of IL-4 and IFN-γ in T-cell supernatants are undetectable with an enzyme-linked immunosorbent assay (ELISA) assay, the concentration of these cytokines below the detectable level can significantly increase PDE activity of monocytes in a synergistic and dose-dependent manner. These results suggest that cytokine-mediated activation of monocytes can increase PDE activity. Furthermore, lymphokines may play an important role in modulating the cyclic nucleotide regulatory pathway.