A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitor.
BACKGROUND
Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.


OBJECTIVE
Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.


METHODS
CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.


CONCLUSIONS
CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.
Institute of Disease Control and Prevention, Academy of Military Medical Science, Beijing 100071, China.
Chuanfu
C
Zhang
Yuanyong
Y
Xu
Leili
L
Jia
Yutao
Y
Yang
Yong
Y
Wang
Yansong
Y
Sun
Liuyu
L
Huang
Fei
F
Qiao
Stephen
S
Tomlinson
Xuelin
X
Liu
Yusen
Y
Zhou
Hongbin
H
Song
D000818:Animals; D001688:Biological Products / Q000235:genetics / Q000627:therapeutic use; D018957:CD59 Antigens / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007251:Influenza, Human / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D008168:Lung / Q000473:pathology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000473:pathology; D011951:Receptors, Complement / Q000235:genetics / Q000627:therapeutic use; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D016019:Survival Analysis
D001688:Biological Products; D018957:CD59 Antigens; C081470:Cr1l protein, mouse; D007166:Immunosuppressive Agents; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D011993:Recombinant Fusion Proteins