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APT070 (Mirococept), a membrane‐localised complement inhibitor, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury
Author(s) -
Souza Danielle G,
Esser Dirk,
Bradford Roberta,
Vieira Angélica T,
Teixeira Mauro M
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706286
Subject(s) - ischemia , pharmacology , medicine , reperfusion injury , complement system , complement membrane attack complex , vascular permeability , inflammation , immunology , antibody
1 Activation of the complement system has been shown to play a major role in the mediation of reperfusion injury. Here, we assessed the effects of APT070 (Mirococept), a novel membrane‐localised complement inhibitor based on a recombinant fragment of soluble CR1, on the local, remote and systemic injuries following intestinal ischaemia and reperfusion (I/R) in the rat. 2 In a model of mild I/R injury (30 min of ischaemia and 30 min of reperfusion), APT070 dose‐dependently (1–10 mg kg −1 ) inhibited the increase in vascular permeability of and neutrophil influx into intestine and lungs. Maximal inhibition occurred at 10 mg kg −1 . 3 Following severe I/R injury (120 min of ischaemia and 120 min of reperfusion), APT070 (10 mg kg −1 ) markedly prevented neutrophil influx and the increase in vascular permeability both in the intestine and the lungs. 4 APT070 also effectively suppressed the increase of tissue (intestine and lungs) and serum concentrations of TNF‐ α and IL‐6, but not those of IL‐1 β or IL‐10. There was no significant reduction of mortality in the APT070 group. 5 In conclusion, treatment with the membrane‐targeted complement inhibitor APT070 significantly reduced the hyperinflammatory response after mild and severe ischaemia and reperfusion injury (I/RI) in rats. APT070 may be effective in therapeutic indications involving gut I/RI.British Journal of Pharmacology (2005) 145 , 1027–1034. doi: 10.1038/sj.bjp.0706286 ; published online 13 June 2005