Borges W G, Augustine N H, Hill H R
Departments of Pathology, Pediatrics, and Medicine, University of Utah School of Medicine, and the ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84132, USA.
J Pediatr. 2000 Feb;136(2):176-80. doi: 10.1016/s0022-3476(00)70098-9.
Patients with the hyperimmunoglobulinemia E (hyper-IgE) syndrome are reported to have defective production of interferon gamma (IFN-gamma). Because IFN-gamma is a major activator of polymorphonuclear leukocytes (PMNs), this could result in defective PMN chemotaxis and markedly elevated IgE levels because of the unopposed action of interleukin (IL)-4. IL-12, an important enhancer of IFN-gamma production, also suppresses IgE production. This study assessed the IL-12/IFN-gamma pathway in patients with hyper-IgE syndrome.
Production of IL-12 and IFN-gamma by mononuclear cells from 10 patients with hyper-IgE syndrome in response to a number of stimuli was determined, as well as the effect of IL-12 on IFN-gamma release and cell proliferation.
IL-12 and IFN-gamma production by the patients' cells was similar to that of control subjects independent of the stimulus used, except for Staphylococcus aureus, with which cells of patients with hyper-IgE syndrome released markedly less IFN-gamma (19.8%; P <.002). The ability of recombinant IL-12 to enhance IFN-gamma release from patients' cells in response to all stimuli was, however, significantly lower than with control cells (12% to 51%; P <.03).
The lymphocytes of patients with hyper-IgE syndrome have an impaired response to IL-12, resulting in decreased IFN-gamma production, which may be of key importance in the pathogenesis of the immune abnormalities of hyper-IgE syndrome.
据报道，高免疫球蛋白E（高IgE）综合征患者的干扰素γ（IFN-γ）产生存在缺陷。由于IFN-γ是多形核白细胞（PMN）的主要激活剂，这可能导致PMN趋化性缺陷，并因白细胞介素（IL）-4的无对抗作用而使IgE水平显著升高。IL-12是IFN-γ产生的重要增强剂，也可抑制IgE产生。本研究评估了高IgE综合征患者的IL-12/IFN-γ途径。
测定了10例高IgE综合征患者的单核细胞在多种刺激下产生IL-12和IFN-γ的情况，以及IL-12对IFN-γ释放和细胞增殖的影响。
患者细胞产生IL-12和IFN-γ的情况与对照受试者相似，与所用刺激无关，但金黄色葡萄球菌刺激除外，高IgE综合征患者的细胞释放的IFN-γ明显较少（19.8%；P<.002）。然而，重组IL-12增强患者细胞对所有刺激释放IFN-γ的能力明显低于对照细胞（12%至51%；P<.03）。
高IgE综合征患者的淋巴细胞对IL-12反应受损，导致IFN-γ产生减少，这可能在高IgE综合征免疫异常的发病机制中起关键作用。
