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Background  Mosquitoes are armed with physiologically active compounds to suppress the host immunity including host inflammatory reaction. However, the specific anti-inflammatory components in mosquitoes remain unknown.    Results  By searching for the immunomodulatory molecules from the mosquito  Aedes aegypti  (Diptera: Culicidae) at NCBI for anti-inflammatory function, five cecropins (for short in this study:  Aeae Cec1, 2, 3, 4 and 5) were selected.  Aeae Cec1-5 efficiently inhibited the expression of inducible nitric oxide synthase (iNOS), nitrite, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and human peripheral blood mononuclear cells (PBMCs) with low toxicity to mammalian cells. Among the five analogues,  Aeae Cec5 had the strongest anti-inflammatory activity, and generated an additive effect with other  Aeae Cec peptides. In a mouse model of endotoxin shock,  Aeae Cec1-5 effectively reduced TNF-α, IL-1β and IL-6 expression in lungs, serum and peritoneal lavage and correspondingly reduced lung damage and edema, with  Aeae Cec5 showing the best protection. In mice infected with  Escherichia coli  or  Pseudomonas aeruginosa , administration of  Aeae Cec5 reduced the production of TNF-α, IL-1β and IL-6 and correspondingly reduced lung tissue damage. These effects of  Ae. aegypti Aeae Cec1-5 were attributed to an efficient inhibition of the activation of mitogen-activated protein kinases (MAPKs) and transcriptional nuclear factor-κB (NF-κB) signaling pathways, as well as partial neutralization of LPS.    Conclusions  The current work characterized the specific anti-inflammatory agents in  Ae. aegypti  and provided  Aeae Cec5 as a potent anti-endotoxin peptide that could serve as the basis for the development of anti-inflammatory therapy.    Electronic supplementary material  The online version of this article (10.1186/s13071-018-3000-8) contains supplementary material, which is available to authorized users.

Anti-inflammatory activities of Aedes aegypti cecropins and their protection against murine endotoxin shock