Ward B J, Johnson R T, Vaisberg A, Jauregui E, Griffin D E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Clin Immunol Immunopathol. 1991 Nov;61(2 Pt 1):236-48. doi: 10.1016/s0090-1229(05)80027-3.
In natural measles virus infection, evidence of intense immune system activation is present simultaneously with clinically relevant immune suppression. While evidence of activation is most prominent early in the disease, skin test responses and in vitro lymphoproliferation are depressed for weeks after the onset of the rash. It is not known whether the prolonged period of reduced immune responsiveness results from a single defect or a succession of different abnormalities. To gain further insight into measles-induced immune suppression we studied the production of soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN-gamma), IL-1 beta, and tumor necrosis factor (TNF alpha) by peripheral blood mononuclear cells (PBMC) isolated from measles patients at various times after the onset of the rash. Studies included addition of supplemental recombinant IL-1 beta (rIL-1 beta) or recombinant IL-2 (rIL-2) or suppression of prostaglandin synthesis by indomethacin (IM). Proliferation in response to phytohemagglutin (PHA) was abnormal at all stages of disease. During the acute phase (first week after the onset of the rash) spontaneous production of sIL-2R was increased (76 +/- 54 vs. controls 4 +/- 4; P less than 0.03), suggesting in vivo T cell activation while PHA-induced sIL-2R was decreased (228 +/- 43 vs. control 582 +/- 127; P less than 0.002), suggesting that the capacity to produce IL-2 in response to mitogen was limited. Supplementation of PHA-stimulated cultures with rIL-2 improved but did not normalize both proliferation (58,600 +/- 4900 to 70,700 +/- 4400 vs. control 97,700 +/- 15,500; P less than 0.03) and sIL-2R levels (114 +/- 58 to 309 +/- 87 vs. control 582 +/- 127; P less than 0.003). Both spontaneous (25 +/- 18 vs. control 237 +/- 92; P less than 0.002) and PHA-induced (20 +/- 20 vs. control 604 +/- 129; P less than 0.004) TNF alpha levels were subnormal and were not improved with rIL-2, rIL-1 beta, or IM, suggesting a block in monocyte TNF alpha production. Spontaneous and PHA-induced IFN-gamma and IL-1 beta levels were normal. During the convalescent phase (greater than 2 weeks after the onset of the rash), spontaneous levels of sIL-2R were normal and PHA-induced levels were completely normalized with supplemental rIL-2 but proliferation remained below normal.(ABSTRACT TRUNCATED AT 400 WORDS)
在自然感染麻疹病毒的过程中，免疫系统强烈激活的证据与具有临床意义的免疫抑制同时存在。虽然激活的证据在疾病早期最为突出，但皮疹出现后的数周内，皮肤试验反应和体外淋巴细胞增殖均受到抑制。目前尚不清楚免疫反应性降低的延长时期是由单一缺陷还是一系列不同异常导致的。为了进一步深入了解麻疹诱导的免疫抑制，我们研究了从麻疹患者皮疹出现后的不同时间分离出的外周血单核细胞（PBMC）产生可溶性白细胞介素-2受体（sIL-2R）、干扰素-γ（IFN-γ）、白细胞介素-1β（IL-1β）和肿瘤坏死因子（TNFα）的情况。研究包括添加补充重组白细胞介素-1β（rIL-1β）或重组白细胞介素-2（rIL-2），或用吲哚美辛（IM）抑制前列腺素合成。在疾病的所有阶段，对植物血凝素（PHA）的增殖反应均异常。在急性期（皮疹出现后的第一周），sIL-2R的自发产生增加（76±54对对照组4±4；P＜0.03），提示体内T细胞激活，而PHA诱导的sIL-2R降低（228±43对对照组582±127；P＜0.002），提示对有丝分裂原产生IL-2的能力受限。用rIL-2补充PHA刺激的培养物可改善但不能使增殖（58,600±4900至70,700±4400对对照组97,700±15,500；P＜0.03）和sIL-2R水平（114±58至309±87对对照组582±127；P＜0.003）正常化。自发（25±18对对照组237±92；P＜0.002）和PHA诱导（20±20对对照组604±129；P＜0.004）的TNFα水平均低于正常，且用rIL-2、rIL-1β或IM均未改善，提示单核细胞TNFα产生受阻。自发和PHA诱导的IFN-γ和IL-1β水平正常。在恢复期（皮疹出现后超过2周），sIL-2R的自发水平正常，补充rIL-2后PHA诱导的水平完全正常化，但增殖仍低于正常。（摘要截短为400字）
