Lactococcus lactis expressando IL-10 recombinante modula a asma alérgica experimental em camundongos BALB/c

Abstract

Around 300 million people worldwide suffer from asthma, and the prevalence of allergic diseases has increased. Much effort has been employed in the study of mechanisms involved in immune response observed in asthma, to intervene for the treatment of this condition. In the establishment of inflammation in asthma, the Th2 cytokines and eosinophils are essential. For therapeutic interventions against this disease, the interleukin (IL)-10 is an important cytokine because it has central role in the regulation of inflammatory cascades. This work evaluated the immunomodulatory effect of Lactococcus lactis strains expressing recombinant IL-10 in a mice model of ovalbumin (OVA)-induced asthma. The following experimental strains were used: Lactococcus lactis expressing recombinant IL-10 in a cytoplasmic production form (LL CYT) or secretory production form (LL SEC), and wild type (LL WT). Initially, tests were performed to determine production of IL-10 by the recombinant strains and evaluation of immune response triggered by L. lactis wild type. After intranasal administration of lactococos producing recombinant IL-10 and induction of asthma, blood samples were collected to detect immunoglobulin-E anti-OVA and bronchus-alveolar lavage (BAL) was performed for total cell count and inflammatory cell count. Furthermore, the lungs were collected to detect the eoperoxidase activity, determination of cytokines and chemokines, and evaluation of pathology. In modulation analysis, animal groups that received LL CYT and LL SEC strains showed significant reduction in total cells and eosinophils numbers, eoperoxidase activity, IgE level, in the cytokine IL-4 and the chemokine CCL3 levels and in pulmonary inflammation when compared to the ASTHMA group. Only the LL CYT/ASTHMA group showed reduced levels of IL-5, CCL2, CCL5 and CCL11. Treatment with L. lactis producing recombinant IL-10 used in this study (LL CYT and LL SEC) modulated experimental asthma in the mice model, and the LL CYT strain was more efficient in the suppression of allergic inflammation.