Anti-inflammatory Effect And Mechanism Of Avermectin

It has been shown that some macrolide antibiotics such as erythromycin, roxithromycin, azithromycin, ivermectin could regulate inflammatory reaction by affecting bacterial toxic factors or down-regulate proinflammatory cytokines in infectious diseases and immunity inflammatory treatment in addition to used as antibacterials and antiparasite drugs. Avermectin is a hexadeco-dimension macrocyclic lactone compound for insect disinfestations. Its derivate ivermectin has been reported to regulate inflammatory cytokine production. Avermectin has a similar structural formula to ivermectin. Therefore, this paper study on whether avermectin has any anti-inflammatory effect.First, the anti-inflammatory effect of avermectin is completed in vivo. The preventive and therapeutical effect of different concentrations of avermectin on mice was studied using LPS-induced murine septic shock model. The prophylactic trial showed that avermectin had certain preventive effect on septic shock mice. Mice were given avermectin at doses of 1, 2 and 4 mg/kg, survival rates were 16.7 %, 37.5 % and 25.0 %, respectively. The therapeutical test showed that survival rates of mice were 0 %, 25.0 % and 16.7 %, respectively. The result suggested that avermectin effectively improved survival rates in septic shock mice.Then builted LPS-induced inflammatory model using murine RAW 264.7 macrophages, and studied the effect of different concentrations of avermectin on cytokine TNF-α, IL-1β, IL-6 and IL-10 production by sandwich ELISA method. The result showed that avermectin significantly regulated TNF-α, IL-1βand IL-10 levels, but had little inhibitory effect on IL-6.The mechanism of LPS-induced cytokine has been extensively studied, there are several typical signal pathways participating in this process, NF-κB and MAPKs are the most classical pathways. Therefore, the effect of avermectin on NF-κB and MAPKs signal pathways was determined by western blotting and immunofluorescence methods in LPS-induced murine RAW 264.7 macrophages. The results showed that avermectin suppressed LPS-induced proinflammatory cytokine production by inhibiting the activation of both JNK,p38 MAPKs and NF-κB p65 into nucleus.In conclusion, the results suggested that avermectin suppressed LPS-induced proinflammatory cytokine production by inhibiting the activation of both NF-κB and MAPKs pathways, and improved the survival rate in LPS-induced septic shock mice.