Background. CF airway inflammation is related to genetic CFTR defect and to dysregulation of iron homeostasis and it can precede bacterial infection. Bacterial infections are favored by iron overload thus worsening inflammation and cell damage. A dangerous vicious circle involving inflammation damage, bacterial infection, and dysregulation of iron homeostasis, is established in CF airways.

Hypothesis and objectives. We hypothesize that lactoferrin (Lf), an iron-chelating glycoprotein of the innate immunity of human secretions, could be a key molecule exerting anti-inflammatory and anti-microbial activities interrupting the vicious circle. Our results show that Lf administered by aerosol reduces inflammation and infection in pre-clinical mouse models of acute and chronic lung infection. Since in airways secretions Lf activity can be reduced by proteolytic enzymes, Lf-liposomes have been prepared to protect Lf against proteolytic activity.