Inhibition of lipopolysaccharide-induced inflammation by nippostrongylus brasiliensis larvae and excretory-secretory products (es)

Nippostrongylus brasiliensis is a rodent intestinal nematode with an important pulmonary migrating stage. Previous studies have observed a lack of TNF-α production and minimal recruitment of neutrophils, which led us to the belief that anti-inflammatory mechanisms could be active in the lung stage. In this study, lipopolysaccharide (LPS) stimulated alveolar macrophages (NR8383) or rat lungs were used as in vitro or in vivo inflammation models respectively. Both live N.brasiliensis larvae and NES significantly reduced the production of LPS-induced pro-inflammatory mediators, TNF-α and NO, but not IL-1β, in NR8383 cells. The inhibition of TNF-α production was related to the heatlabile and trypsin-sensitive fraction of NES concentrate. 1-D protein gel of NES concentrate revealed that the molecular weights of proteins are between 6kDa and 100kDa. Glycoproteins were found abundant in NES concentrate. The inflammatory processes, including NF-κB translocation and TNF-α gene transcription were significantly inhibited by NES and/or NES concentrate. In vivo, we observed a significant reduction of neutrophil recruitment (≈ 40%) by NES on a background of LPS (100ng/ml) induced inflammation. This reduction was associated with the significant inhibition in gene transcriptions of proinflammatory mediators TNF-α, IL-1β, iNOS, ICAM-1 and MIP-2 in bronchoalveolar lavage (BAL) cells. The down-regulation of pro-inflammatory mediators and inflammatory processes observed in this study suggests that N.brasiliensis larvae and/or NES are capable of modifying the normally potent LPS inflammatory response, both in vitro and in vivo. This study and planned future studies could be fundamental in developing anti-inflammatory agents with immune-active molecules in N.brasiliensis-derived products.