We found that IL-1Ra levels in BALF

of IPF patients were increased, but this was not enough to equal the vast increase in local IL-1β. selleck Altogether, this resulted in a 3·5-fold decrease in the IL-1Ra/IL-1β ratio in IPF patients compared to healthy controls. In animal studies it has been shown that alterations in the balance between IL-1β and IL-1Ra cause the development of lung fibrosis. Mice with bleomycin-induced fibrosis have an up-regulated expression of IL-1β mRNA after instillation of bleomycin [20], and addition of recombinant IL-1β induces fibrotic remodelling [8]. Overexpression of IL-1β in rat lungs after intratracheal administration of bleomycin was associated with severe progressive tissue fibrosis

in the lung, characterized by the presence of myofibroblasts, fibroblast foci and significant extracellular accumulations of collagen and fibronectin [4]. Other studies showed that administration of exogenous IL-1Ra prevented or even reversed the generation of pulmonary and synovial fibrosis [21–23]. The pathogenetic processes in bleomycin-induced fibrosis are simply a model for IPF and results cannot be extrapolated to human IPF. However, in patients with acute myocardial infarction, there is evidence that IL-1 blockade with IL-1Ra see more suppresses the inflammatory response and positively affects tissue remodelling [24]. IL-1 ligands such as IL-1α, IL-1β and IL-1Ra all bind to the IL-1 receptor (IL-1R1). Mice lacking the IL-1R1 receptor showed significantly reduced cellular infiltrates, alveolar wall destruction and collagen deposition.

Moreover, blockade of the IL-1R1 receptor by exogenous IL-Ra (anakinra) dramatically reduced neutrophil influx and the formation of bleomycin-induced fibrosis in mice [8]. Altogether, IL-1 seems to be a critical cytokine and may possibly be a therapeutic target in IPF. There are different hypotheses Glycogen branching enzyme about the role of inflammation and thus proinflammatory cytokines such as IL-1β in the role of pulmonary fibrosis. Historically, the hypothesis was that inflammation in response to an unknown agent was the key process in IPF, ultimately resulting in fibrosis. The current concept is that IPF is a result of repeated episodes of lung injury, with a minor role for inflammation. This concept states that inflammation in IPF could be a consequence of the architectural remodelling, rather than a cause. The increased parameters of inflammation such as neutrophilia in BALF may be a reflection of remodelling and traction bronchiectasis due to fibrosis [25]. However, this does not exclude a role for inflammation in an earlier stage of the disease. An interesting paper in this context is the study by Flaherty et al.