Byron K A, Liberatos S, Varigos G A, Wootton A M
Department of Biochemistry, Royal Melbourne Hospital, Parkville, Australia.
Int Arch Allergy Immunol. 1992;99(1):50-5. doi: 10.1159/000236335.
Peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have a reduced capacity to produce interferon-gamma (IFN-gamma) in vitro, in response to phytohaemagglutinin (PHA) when compared to healthy non-atopic controls. This defect appears to correlate closely with the severity of AD at the time of sampling, with less IFN-gamma being produced by cells from patients with more severe disease. Enhanced production of IFN-gamma was observed as the patients clinical symptoms improved. In addition, IFN-gamma production could be increased by either pre-culturing the cells for 3 days prior to PHA stimulation or by addition of indomethacin to the culture medium. These observations suggest that the mechanism of reduced IFN-gamma production in AD is unlikely to be due to an intrinsic cellular defect. The possibility that prostaglandins mediate the suppressed production of IFN-gamma in AD was supported by demonstrating that exogenous prostaglandin E2 (PGE2) inhibited IFN-gamma production in PHA-stimulated PBMC. PGE2 at a physiological concentration (10(-9) M) was also shown to enhance interleukin 4 induction of IgE synthesis by PBMC cultures. Our data suggest that alterations in prostaglandin metabolism play a crucial role in the pathogenesis of AD by inhibiting the production of IFN-gamma.
与健康的非特应性对照相比，特应性皮炎（AD）患者的外周血单个核细胞（PBMC）在体外对植物血凝素（PHA）反应时产生干扰素-γ（IFN-γ）的能力降低。这种缺陷似乎与采样时AD的严重程度密切相关，病情越严重的患者细胞产生的IFN-γ越少。随着患者临床症状改善，观察到IFN-γ产生增加。此外，在PHA刺激前将细胞预培养3天或在培养基中添加吲哚美辛均可增加IFN-γ的产生。这些观察结果表明，AD中IFN-γ产生减少的机制不太可能是由于内在的细胞缺陷。通过证明外源性前列腺素E2（PGE2）抑制PHA刺激的PBMC中IFN-γ的产生，支持了前列腺素介导AD中IFN-γ产生受抑制的可能性。生理浓度（10^(-9) M）的PGE2还显示可增强PBMC培养物中白细胞介素4诱导的IgE合成。我们的数据表明，前列腺素代谢的改变通过抑制IFN-γ的产生在AD的发病机制中起关键作用。
