A Recombinant Cystatin from Ascaris Lumbricoides Has Immunomodulatory Effects
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Sandra M Coronado, Luis Barrios, Josefina Zakzuk, Luis Franco, Luis Caraballo, MD PhD
Rationale: Helminthiasis may ameliorate inflammatory chronic diseases, such as inflammatory bowel disease (IBD) and asthma. Information about immunomodulators from Ascaris lumbricoides, the most common human helminth worldwide is scarce, but could be important considering the co-evolutionary relationships between helminths and humans. We sought to evaluate the potential immunomodulatory effects of a cystatin from A. lumbricoides on an acute model of IBD. 

Methods: From an A. lumbricoides cDNA library we obtained an E. coli produced recombinant cystatin (rAl-CPI). Protease activity inhibition was tested on cathepsin B and papain. Immunomodulatory effects were evaluated at two doses, administered intraperitoneally (0.5 and 0.25 µg/g) on mice with chemically induced (4% Dextran Sodium Sulphate, DSS) - IBD. Body weight, colon length, disease activity index (DAI), histological inflammation score, myeloperoxidase (MPO) activity and gene expression of six cytokines in colon tissue were analyzed.

Results: rAl-CPI showed biological activity. The treatment with rAl-CPI significantly reduced DAI, MPO activity and inflammation score, without toxic effects. Also, IL-10 (p<0.0001) and TGFβ (p=0.001) gene overexpression was observed in rAl-CPI treated (both concentrations) compared to DSS-exposed animals and healthy (PBS) group. Furthermore, a significant reduction of IL-6 (p<0.001) and TNFα (p<0.01) expression, key mediators of IBD, was observed. Although lower expression of IL-1β and IL-12 was detected, it was not statistically significant.

Conclusions: rAl-CPI reduces the inflammation in a mouse model of IBD, probably by increasing the expression of anti-inflammatory cytokines and reducing pro-inflammatory ones. The usefulness of this recombinant protein in respiratory inflammation should be further investigated.