Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness:: innate vs. adaptive immune response
Lamellar pro-inflammatory cytokine expression patterns in laminitis at the developmental stage and at the onset of lameness:: innate vs. adaptive immune response
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DOI：
10.2746/042516407x155406
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发表时间：
2007-01-01
影响因子：
2.2
通讯作者：
Pollitt, C. C.
中科院分区：
文献类型：
--
作者：
Belknap, J. K.;Giguere, S.;Pollitt, C. C.
进行研究的原因：最近的研究表明炎症在板层炎的早期阶段发挥作用，与人类脓毒症中的器官衰竭类似，早期炎症机制可能导致下游事件导致板层衰竭。免疫反应类型（即先天性与适应性）的表征对于制定应对这些有害事件的治疗策略至关重要。目的：使用黑核桃提取物 (BWE) 和低聚果糖 (OF) 蹄叶炎模型，定量已知在蹄叶炎早期阶段的先天性和适应性免疫反应中重要的促炎细胞因子的基因表达。方法：使用实时 qPCR 评估板层发育阶段和跛行开始时白细胞介素-1β、2、4、6、8、10、12和18以及肿瘤坏死因子α和干扰素γ的mRNA表达。结果：在BWE模型的发育阶段以及BWE模型和跛行开始时，先天免疫反应中重要的细胞因子的层状mRNA表达显着增加。的模型。在适应性免疫反应的 Th1 和 Th2 臂的细胞因子特征中，BWE 模型中急性跛行发生时出现混合反应，而 OF 模型中跛行发生时反应偏向 Th1 反应。以及跛行开始时的先天性和适应性免疫反应的混合。潜在相关性：这些结果表明，早期蹄叶炎（以及有患蹄叶炎风险的马）的抗炎治疗不仅应包括解决前列腺素活性的治疗药物，还应解决板层细胞因子表达的显着增加。
Reasons for performing study: Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure in human sepsis, early inflammatory mechanisms may lead to downstream events resulting in lamellar failure. Characterisation of the type of immune response (i.e. innate vs. adaptive) is essential in order to develop therapeutic strategies to counteract these deleterious events.Objectives: To quantitate gene expression of pro-inflammatory cytokines known to be important in the innate and adaptive immune response during the early stages of laminitis, using both the black walnut extract (BWE) and oligofructose (OF) models of laminitis.Methods: Real-time qPCR was used to assess lamellar mRNA expression of interleukins-1 beta, 2, 4, 6, 8, 10, 12 and 18, and tumour necrosis factor alpha and interferon gamma at the developmental stage and at the onset of lameness.Results: Significantly increased lamellar mRNA expression of cytokines important in the innate immune response were present at the developmental stage of the BWE model, and at the onset of acute lameness in both the BWE model and OF model. Of the cytokines characteristic of the Th1 and Th2 arms of the adaptive immune response, a mixed response was noted at the onset of acute lameness in the BWE model, whereas the response was skewed towards a Th1 response at the onset of lameness in the OF model.Conclusions: Lamellar inflammation is characterised by strong innate immune response in the developmental stages of laminitis; and a mixture of innate and adaptive immune responses at the onset of lameness.Potential relevance: These results indicate that antiinflammatory treatment of early stage laminitis (and the horse at risk of laminitis) should include not only therapeutic drugs that address prostanoid activity, but should also address the marked increases in lamellar cytokine expression.