Parameters used in HTStream preprocessing.

Bovine respiratory syncytial virus (BRSV) infection is a part of the bovine respiratory disease complex. This is one of the most significant problems in both the dairy and beef production sector, inflicting severe economic damage to the industry. BRSV manifests clinically as a respiratory syndrome, affecting both upper and lower respiratory tract, including bronchiolitis with dyspnea and wheezing. It has been shown previously that these symptoms caused by IL-4/IL-13 domination in the immune response are associated with an antibody isotype switch to IgE. Prostaglandin production, such as PGE2 is another factor contributing to the pathogenesis of the disease. In this work we demonstrated the effects of ibuprofen and antiviral fusion protein inhibitor (FPI) separately and combined. We showed the synergistic effect of ibuprofen in combination with FPI on antiviral effects and suppression of PGE2, resulting in improved cytoplasmic toll-like receptor recognition and humoral immune responses mediated by antimicrobial peptide in lungs. We also demonstrated a Th1/Th2 balance shift towards a Th2 response in lungs and mediastinal lymph nodes, favorable to IL-4/IL-13 responses. This shift may explain the factors contributing to higher viral loads and the lack of histopathological improvement with ibuprofen administered without FPI. Additionally, we demonstrated that endocannabinoids may play a crucial role as natural regulators of the inflammation, adaptive immune response, and resolution of the inflammatory process.牛呼吸道合胞病毒（Bovine respiratory syncytial virus, BRSV）感染是牛呼吸道疾病复合征的组成部分。该问题是乳品养殖与肉牛养殖行业中最严峻的挑战之一，给产业造成了巨额经济损失。BRSV的临床表现为呼吸道综合征，可累及上下呼吸道，引发伴有呼吸困难与喘息的细支气管炎。既往研究表明，由免疫应答中IL-4/IL-13主导所引发的此类症状，与抗体类别转换为IgE密切相关。前列腺素（如前列腺素E2, PGE2）的生成是推动该疾病发病机制的另一关键因素。本研究分别考察了布洛芬与抗病毒融合蛋白抑制剂（FPI）的单独作用及联合应用效果。结果证实，布洛芬与FPI联合使用可产生协同抗病毒效应，并抑制PGE2生成，进而改善胞质Toll样受体（Toll-like receptor, TLR）识别能力，以及肺部抗菌肽介导的体液免疫应答。此外，本研究发现肺部与纵隔淋巴结内的Th1/Th2平衡向Th2应答偏移，这一偏移有利于IL-4/IL-13介导的免疫反应。该偏移可解释为何未联合FPI仅使用布洛芬时，无法有效降低病毒载量且未能实现组织病理学改善。最后，本研究证实内源性大麻素（endocannabinoids）可作为炎症、适应性免疫应答及炎症消退过程的天然调节剂发挥关键作用。