Comparison of the therapeutic effect of SYN008 with Xolair? in allergic asthma mice:inflammation and remodeling
Objective To compare the efficacy of omalizumab analogue(SYN008)with omalizumab original drug(Xolair®)in allergic asthma mice model,providing a basis for the clinical application of SYN008.Methods Forty healthy BALB/c mice were divided into four groups,with 10 mice in each.Group I was the control group and asthma was induced by intraperitoneal injection of ovalbumin(OVA)-aluminium hydroxide in groupsⅡ-Ⅳ.Mice in groupsⅢand Ⅳ were treated with Xolair®(200 μg/each)and SYN008(200 μg/each)intraperitoneally,respectively.The levels of IgE in serum and T helper 2 cell(Th2)cytokines in broncho alveolar lavage fluid(BALF)were detected in each group;lung tissues were observed by hematoxylin-eosin(HE)staining,peroxynitrite-schiff(PAS)staining and Mas-son's trichrome(Masson)staining.For the expression of transforming growth factor beta 1(TGF-β1),phosphorylated Smad family member 3(P-smad3)/Smad family member 3(Smad3),collagen Ⅲ(COL3)and mucin 5AC(MUC5AC),lung tissues were examined by quantitative real-time PCR(RT-qPCR),enzyme linked immunosorbent assay(ELISA),western blotting(WB)and immunohistochemistry.Results The levels of IgE in serum and interleu-kin-4(IL-4),IL-5 and IL-13 in BALF were significantly increased in the groupⅡ compared with those in the control group(all P<0.001).The levels of IgE in serum and IL-4/5/13 in BALF in groups Ⅲ and Ⅳ were significantly de-creased compared with those in the groupⅡ(P<0.001,P<0.05,P<0.01,P<0.05;P<0.001,P<0.05,P<0.05,P<0.05).HE,PAS and Masson staining confirmed that Xolair®and SYN008 could effectively reduce inflammatory cell ag-gregation,airway cuprocyte chemotaxis and collagen deposition in mice with asthma.Xolair® and SYN008 could atten-uate airway remodeling by inhibiting TGF-β1,P-smad3/Smad3,COL3 and MUC5AC in lung tissues,with no reach statistical significance between the two groups in all the assays.Conclusion SYN008 improves allergic asthma in mice and is consistent with the efficacy of Xolair®,which is expected to be clinically significant for allergic asthma in the fu-ture.
Omalizumab analogue(SYN008)Omalizumab original drug(Xolair®)Allergic asthmaInflamma-tionRemodeling
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