Finally, in vivo treatment with the KDM6 inhibitor, GSK J4, during RSV infection reduced inflammatory DC in the lungs along with IL-13 levels and overall inflammation.
Infants with rhinovirus had higher levels of NFκB-induced type-2 cytokines (IL-10 and IL-13; FDR<0.01).ConclusionIn infants with bronchiolitis, rhinovirus and RSV infections had different nasal airway microRNA profiles associated with NFκB signaling.
We observed that neonatal RSV infection resulted in an enhanced infiltration of eosinophils and neutrophils in the lungs, in parallel with a significant increase in the levels of IL-5 and IL-13 in bronchoalveolar lavage fluids on day 2 after reinfection.
Consistent with the data from RSV-infected infants, CD4 T cell production of Interleukin (IL)-9, IL-13, and IL-17 has all been shown to contribute to RSV-induced disease in a murine model of RSV infection.
To assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children.
By investigating IL4 and IL13 polymorphisms in 131 children with severe RSV infection and 270 control subjects, we found an association between IL13 polymorphism -1112C/T and severe RSV infection (P = .026).
To demonstrate a causative link, we depleted TLR3-/- mice of IL-13 during RSV infection and found that mucus and gob5 expression in the lungs was attenuated.
Thus, these data suggest that CCR1-mediated responses have a primary role for inducing severe disease during RSV infection, and may be responsible for altering the lung pathophysiological responses to subsequent allergen challenges via IL-13-mediated mechanisms.
In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection.