Vieira L M, Sampaio E P, Nery J A, Duppre N C, Albuquerque E C, Scheinberg M A, Sarno E N
Leprosy Laboratory, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, Brazil.
Rev Inst Med Trop Sao Paulo. 1996 Mar-Apr;38(2):103-11. doi: 10.1590/s0036-46651996000200004.
Recent data suggest that the clinical course of reactional states in leprosy is closely related to the cytokine profile released locally or systemically by the patients. In the present study, patients with erythema nodosum leprosum (ENL) were grouped according to the intensity of their clinical symptoms. Clinical and immunological aspects of ENL and the impact of these parameters on bacterial load were assessed in conjunction with patients' in vitro immune response to mycobacterial antigens. In 10 out of the 17 patients tested, BI (bacterial index) was reduced by at least 1 log from leprosy diagnosis to the onset of their first reactional episode (ENL), as compared to an expected 0.3 log reduction in the unreactional group for the same MDT (multidrug therapy) period. However, no difference in the rate of BI reduction was noted at the end of MDT among ENL and unreactional lepromatous patients. Accordingly, although TNF-alpha (tumor necrosis factor) levels were enhanced in the sera of 70.6% of the ENL patients tested, no relationship was noted between circulating TNF-alpha levels and the decrease in BI detected at the onset of the reactional episode. Evaluation of bacterial viability of M. leprae isolated from the reactional lesions showed no growth in the mouse footpads. Only 20% of the patients demonstrated specific immune response to M. leprae during ENL. Moreover, high levels of soluble IL-2R (interleukin-2 receptor) were present in 78% of the patients. Circulating anti-neural (anti-ceramide and anti-galactocerebroside antibodies) and anti-mycobacterial antibodies were detected in ENL patients' sera as well, which were not related to the clinical course of disease. Our data suggest that bacterial killing is enhanced during reactions. Emergence of specific immune response to M. leprae and the effective role of TNF-alpha in mediating fragmentation of bacteria still need to be clarified.
近期数据表明,麻风病反应状态的临床病程与患者局部或全身释放的细胞因子谱密切相关。在本研究中,结节性红斑型麻风(ENL)患者根据其临床症状的严重程度进行分组。结合患者对分枝杆菌抗原的体外免疫反应,评估了ENL的临床和免疫学方面以及这些参数对细菌载量的影响。在17例接受检测的患者中,有10例从麻风病诊断到首次反应发作(ENL)期间,细菌指数(BI)至少降低了1个对数,而在相同的多药治疗(MDT)期间,未发生反应的组预期降低0.3个对数。然而,在MDT结束时,ENL患者和未发生反应的瘤型麻风患者之间的BI降低率没有差异。因此,尽管在70.6%接受检测的ENL患者血清中肿瘤坏死因子-α(TNF-α)水平升高,但在反应发作时检测到的循环TNF-α水平与BI降低之间没有关系。对从反应性病变中分离出的麻风分枝杆菌的细菌活力评估显示,在小鼠足垫中没有生长。只有20%的患者在ENL期间对麻风分枝杆菌表现出特异性免疫反应。此外,78%的患者中存在高水平的可溶性白细胞介素-2受体(IL-2R)。在ENL患者血清中也检测到循环抗神经(抗神经酰胺和抗半乳糖脑苷脂抗体)和抗分枝杆菌抗体,它们与疾病的临床病程无关。我们的数据表明,在反应期间细菌杀伤作用增强。对麻风分枝杆菌特异性免疫反应的出现以及TNF-α在介导细菌碎片化中的有效作用仍有待阐明。