MODULATION OF MUCOSAL IMMUNITY AGAINST CAMPYLOBACTER-JEJUNI BY ORALLY-ADMINISTERED CYTOKINES

MODULATION OF MUCOSAL IMMUNITY AGAINST CAMPYLOBACTER-JEJUNI BY ORALLY-ADMINISTERED CYTOKINES
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DOI:
10.1128/aac.37.12.2688
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发表时间:
1993-12-01
影响因子:
4.9
通讯作者:
ROLLWAGEN, FM
ROLLWAGEN, FM
中科院分区:
医学2区
文献类型:
--
作者:
BAQAR, S;PACHECO, ND;ROLLWAGEN, FM

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研究了口服重组白细胞介素(rIL)对空肠弯曲菌感染小鼠病程和粘膜免疫功能的影响。在感染前24和6 h以及感染后0、24和48 h给小鼠注射rIL-2、rIL-5和rIL-6。空肠HC,以及随后的免疫应答和肠定植抗性的发展。在该模型中,口服给予的细胞因子保留了它们的生物活性,没有明显的副作用。感染后,从经马槟榔碱处理和未经处理的小鼠收集的粪便样品中的初始细菌计数相似。然而,在感染后48小时内,C.在rIL-6处理的动物的粪便中发现空肠脱落。在rIL-5处理的小鼠中,定殖水平也类似地降低,尽管清除率稍慢。与此相反,rIL-2治疗没有显着影响的殖民水平与对照组相比。与rIL-5或rIL-2治疗的动物相比,口服rIL-6治疗也与增强的肠道和全身弯曲杆菌特异性免疫球蛋白A应答相关。再激发后,所有苦参碱处理组的初始定植均比对照组低约2个对数单位。然而,随着时间的推移,局部感染仅在rIL-2治疗的小鼠中得到控制。rIL-5和rIL-6处理对再攻击后的定殖抗性仅具有边际效应。基于这些结果,似乎rIL-2和rIL-5或rIL-6可以起到调节抗-C的诱导和/或表达的作用。空肠免疫通过不同的机制。
The effect of oral recombinant interleukin (rIL) treatment on the course of Campylobacter jejuni infection and the development of mucosal immunity in mice was investigated. rIL-2, rIL-5, and rIL-6 were administered to mice at 24 and 6 h before infection and at 0, 24, and 48 h after infection with C. jejuni HC, and the subsequent development of an immune response and intestinal colonization resistance were determined. In this model, orally administered cytokines retained their biological activities with no apparent side effects. Following infection, initial bacterial counts in fecal samples collected from cytokine-treated and untreated mice were similar. However, within 48 h of infection a greater than 3-log unit reduction in the number of C. jejuni shed in the feces was found for rIL-6-treated animals. Colonization levels were similarly reduced in rIL-5-treated mice, although the rate of clearance was somewhat slower. In contrast, rIL-2 treatment had no significant effect on colonization levels compared with that in controls. Oral rIL-6 treatment was also associated with enhanced intestinal and systemic Campylobacter-specific immunoglobulin A responses compared with those observed in either rIL-5- or rIL-2-treated animals. Upon rechallenge, initial colonization in all cytokine-treated groups was approximately 2 log units lower than that in controls. However, local infection was controlled only in rIL-2-treated mice over time. rIL-5 and rIL-6 treatment had only a marginal effect on colonization resistance following rechallenge. On the basis of these results, it appears that rIL-2 and rIL-5 or rIL-6 may function to modulate the induction and/or expression of anti-C. jejuni immunity through different mechanisms.