Production Characteristic Of Cytokines In Mice Infected By APP And The Effect Of IL-1? During Infection

Actinobacillus pleuropneumoniae(APP)causes porcine pleuropneumonia,leading to great losses for the pig industry worldwide.Experimental animals are the important tools used to research the mechanism of diseases development and host immune defense.However,it has been a controversial hot topic that whether mice can be used as an animal model of APP infection.Therefore,in order to confirm the feasibility of constructing an APP infection model in mice,the APP5 type L20 strain was used to infect ICR mice,an APP infection group and a control group were established.The clinical symptoms,lung index,pathological changes,colony counts,blood routine analysis of blood and alveolar lavage fluid,and levels of cytokines in serum and alveolar lavage fluid by ELISA were detected after infection.Then,inflammatory cytokines significantly changed were selected,such as TNF-?,IL-1?,and IL-17.And the APP-infected mice were treated with cytokine inhibitors to observe their effects on inflammatory responses in mice.In addition,an APP infection model was constructed using NLRP3 gene-deficient mice to evaluate the role of IL-1? during APP infection.The experimental results showed that the ICR mice in the APP infection group showed a significant difference from the control group.Compared with mice in the control group,mice in the infected group had higher clinical symptom scores,body weight change rate,protein levels in the alveolar lavage fluid,more bacteria and inflammatory cells,more severe pathological changes in lung and more noteworthy inflammatory cytokine levels,including TNF-?,IL-1? and IL-17 and other inflammatory cytokine.This indicated that ICR mice were suitable for constructing APP infection models.Then,the inhibitor Diacerein and SB225002 could effectively reduce clinical symptoms and increase survival rate of mice by inhibiting the inflammatory cytokines IL-1? and IL-8.This showed that cytokine inhibitors could significantly inhibit the production of IL-1? and IL-8,thereby reducing the inflammatory response.Compared to normal mice,NLRP3 null mice had lower clinical symptom scores,less bacterial colonization,but higher lung index and more significantly elevated cytokine levels.It was shown that the reduction of IL-1? in gene-deficient mice reduced the pathological changes,but aggravated the inflammatory response.This study confirmed that ICR mice were suitable for constructing APP infection models,severe inflammatory reactions occurred during APP infection and that IL-1? played an important role in the development of inflammatory responses.This provides an important target for the clinical treatment of APP infection,lays a good theoretical foundation and has important guiding significance.