Animal models for analysis of hypersensitivity reactions to Shuanghuanglian injection

Peng Xiao; Li Hou; Zhaohua Liu; Yanling Mu; Zengxiang Liu; Jiao Wang; Shidong Qiu

doi:10.1016/j.molimm.2020.03.014

Animal models for analysis of hypersensitivity reactions to Shuanghuanglian injection

Mol Immunol. 2020 Apr 14:122:62-68. doi: 10.1016/j.molimm.2020.03.014. Online ahead of print.

Authors

Peng Xiao¹, Li Hou², Zhaohua Liu³, Yanling Mu⁴, Zengxiang Liu², Jiao Wang⁵, Shidong Qiu⁶

Affiliations

¹ Shandong Jianzhu University, Jinan, China.
² Shandong Quality Inspection Center for Medical Devices, Jinan, China.
³ School of Pharmaceutical Sciences, Shandong University, Jinan, China.
⁴ Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
⁵ Qilu Hospital of Shandong University, Jinan, China.
⁶ Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. Electronic address: qiushidong@hotmail.com.

PMID: 32302806
DOI: 10.1016/j.molimm.2020.03.014

Abstract

Among a variety of traditional Chinese medicines, Shuanghuanglian injection (SHLI), has the highest incidence of injection-induced immediate hypersensitivity reactions (IHRs). However, the precise mechanisms of SHLI-induced IHRs remain to be understood. In the present study, we characteriszed IHRs as induced by SHLI by recording changes in physiological and hemodynamic indicators following intravenous injections of SHLI in rats and dogs. The results indicate that SHLI induced the release of histamine, decreased mean arterial blood pressure (MAP), increased SC5b-9 in rats and dogs, increased C4d and Bb in dogs without any changes in IgE. n vitro incubation of SHLI with serum from dogs in the presence of an inhibitor of complement activation (EGTA/Mg²⁺) resulted in an increase in C4d. These results suggest that SHLI induces anaphylactoid reactions in rats and dogs. Furthermore, SHLI appears to activate the complement system through classical and alternative pathways in dogs in vivo. Additional experiments in mice demonstrated that SHLI induces locus coeruleus infiltration and results in significant increase in vascular permeability within the skin of mice. We established a reliable method for the evaluation of anaphylactoid reactions induced by complex compounds, using multiple physiological indicators, different experimental models in vivo and in vitro.

Keywords: Anaphylactoid reaction; Animal models; SC5b-9; Shuanghuanglian injection; Vascular permeability.