The versatile nature of MIF (macrophage migration inhibitory factor) in chronic lung diseases

Abstract

Chronic inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma are progressive conditions affecting millions of people worldwide. In order to provide better therapeutic opportunities for COPD and asthma patients we need to explore and understand the contributions of the various cells and proteins involved in these diseases. The aim of the work described in this thesis was to study the expression and function of macrophage migration inhibitory factor (MIF) in COPD and asthma, as this protein influences cellular functions and immune responses and is said to be a pro-inflammatory mediator important in inflammatory lung disease. Here we integrated a critical review of the literature with an experimental approach and showed that while MIF is associated with chronic inflammatory lung diseases, its role is not necessarily proinflammatory, as previously suggested. We found that MIF expression in lung tissue of COPD patients is higher than in control individuals and that MIF expression may be caused by cellular senescence. Additionally we found that MIF expression in the lung is influenced by genetic elements, although not specifically in COPD patients. We also found that the MIF expression in the asthmatic lung is lower than in healthy conditions, and that its expression is associated with the presence of certain innate immune cells involved in allergic inflammatory responses. The work described in this thesis has established a basis for future studies that can unravel the versatile nature of MIF and investigate its true potential in therapeutic strategies for lung diseases.