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2018 ; 46
(5
): e419-e425
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Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential
Clinical Application
#MMPMID29293144
Sun S
; Jiang Y
; Wang R
; Liu C
; Liu X
; Song N
; Guo Y
; Guo R
; Du L
; Jiang S
; Li Y
; Qiu Z
; Zhao G
; Zhou Y
Crit Care Med
2018[May]; 46
(5
): e419-e425
PMID29293144
show ga
OBJECTIVES: Complement activation product C5a plays a critical role in systemic
inflammatory response syndrome induced by viruses, bacteria, and toxic agents
including paraquat poisoning. This study is to explore the efficiency of
anti-C5a-based intervention on systemic inflammatory responses induced by
paraquat poisoning. DESIGN: Study of cynomolgus macaque model and plasma from
paraquat-poisoning patients. SETTING: Laboratory investigation. SUBJECTS:
Cynomolgus macaque (n = 12) and samples of plasma from patients (n = 16).
INTERVENTIONS: The neutralizing antihuman C5a antibody (IFX-1) was administered
to investigate the new treatment strategy for paraquat-induced systemic
inflammatory responses in cynomolgus macaque model. In addition, C5a activation
in plasma of paraquat patients was blocked by IFX-1 to investigate the blockade
role of anti-C5a antibody in activation of inflammatory cells. MEASUREMENTS AND
MAIN RESULTS: Dysregulated complement activation and the subsequent cytokine
storm were found in patients with acute lung injury and in a primate model of
paraquat poisoning. Targeted inhibition of C5a by IFX-1 led to marked alleviation
of systemic inflammatory responses and multiple organ damage in the primate
model. In addition, blockade of C5a activity in plasma from patients completely
inhibited activation of CD11b on blood granulocytes from normal donors,
suggesting that IFX-1 may alleviate the excessive activation of inflammatory
responses and have clinical utility for patients with acute lung injury.
CONCLUSIONS: Anti-C5a antibodies such as IFX-1 may be used as effective
therapeutics for treatment of those suffering from systemic inflammatory
responses induced by chemical poisoning like paraquat.