Fitzsimmons Colin M, Joseph Sarah, Jones Frances M, Reimert Claus M, Hoffmann Karl F, Kazibwe Francis, Kimani Gachuhi, Mwatha Joseph K, Ouma John H, Tukahebwa Edridah M, Kariuki Henry C, Vennervald Birgitte J, Kabatereine Narcis B, Dunne David W
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Infect Immun. 2004 Jul;72(7):4023-30. doi: 10.1128/IAI.72.7.4023-4030.2004.
Chemotherapy for blood-dwelling schistosomes kills the worms and exposes parasite antigen to the circulation. In many people from areas of endemicity, this treatment increases parasite-specific immunoglobulin E (IgE) and other Th2 responses in the months following therapy, responses that have been associated with subsequent resistance to reinfection. Here we investigate much earlier changes in immune reactions after praziquantel therapy in Schistosoma mansoni-infected fishermen working in an area of high transmission in Uganda. The subjects gave blood before treatment and at 1 and 21 days posttreatment. Blood cultures were incubated with schistosome soluble worm antigen (SWA) or soluble egg antigen (SEA). Interleukin-4 (IL-4), IL-5, IL-10, IL-13, gamma interferon, and transforming growth factor beta levels were measured in the cultures and in plasma. A marked transient increase in plasma IL-5 levels was observed in 75% of the subjects (n = 48) by 1 day posttreatment. This response was dependent on pretreatment intensity of infection and was accompanied by a transient decrease in eosinophil numbers. One day posttreatment, blood cultures from the 16 subjects with the greatest increase in plasma IL-5 level (>100 pg/ml) displayed reduced IL-5, IL-13, and IL-10 responses to SWA, and in contrast to the rest of the cohort, these high-IL-5 subjects displayed reduced levels of SWA-specific IgE in plasma 21 days posttreatment. Twenty months after treatment, the intensity of reinfection was positively correlated with the increase in plasma IL-5 level seen 1 day posttreatment. These studies describe the heterogeneity in early immune reactions to treatment, identifying subgroups who have different patterns of reaction and who may have different capacities to mount the responses that have been associated with resistance to reinfection.
针对寄生于血液中的血吸虫的化疗可杀死虫体,并使寄生虫抗原暴露于循环系统。在许多血吸虫病流行地区的人群中,这种治疗会在治疗后的数月内增加寄生虫特异性免疫球蛋白E(IgE)及其他Th2反应,这些反应与随后对再感染的抵抗力有关。在此,我们调查了在乌干达高传播地区工作的曼氏血吸虫感染渔民接受吡喹酮治疗后免疫反应的更早变化。研究对象在治疗前、治疗后1天和21天采集血液。血液培养物与血吸虫可溶性虫体抗原(SWA)或可溶性虫卵抗原(SEA)一起孵育。检测培养物和血浆中的白细胞介素-4(IL-4)、IL-5、IL-10、IL-13、γ干扰素和转化生长因子β水平。75%的研究对象(n = 48)在治疗后1天血浆IL-5水平出现明显的短暂升高。这种反应取决于治疗前的感染强度,同时伴有嗜酸性粒细胞数量的短暂减少。治疗后1天,血浆IL-5水平升高幅度最大(>100 pg/ml)的16名研究对象的血液培养物对SWA的IL-5、IL-13和IL-10反应降低,与其他研究对象不同的是,这些高IL-5水平的研究对象在治疗后21天血浆中SWA特异性IgE水平降低。治疗20个月后,再感染强度与治疗后1天血浆IL-5水平的升高呈正相关。这些研究描述了治疗早期免疫反应的异质性,确定了具有不同反应模式、可能具有不同能力产生与抵抗再感染相关反应的亚组。