This pleads for a hypothesis in which UIP and NSIP are two different entities in one continuum.

Before discarding the role of inflammation in the pathogenesis of IPF, we first need to understand the natural history of UIP [27]. Our hypothesis www.selleckchem.com/products/epz-6438.html states the association of a SNP in the IL1RN gene with IPF predisposition; this suggests a role for IL-1 in the beginning of the pathogenetic process. The present study is one of the more expanded studies evaluating IL-1Ra and IL-1β cytokine polymorphisms and corresponding protein levels in IPF. However, a limitation of this study is that the number of IPF patients is relatively small for genetic associations. Conversely, the results are in line with previously published literature [6,28]. Although our data Tamoxifen supplier suggest no effect of age or gender on the IL-1Ra/IL-1β ratio (results not shown), more studies are needed to confirm the role of a decreased ratio in IPF. Another point that needs attention is that the rs2637988 polymorphism influenced the IL-1Ra/IL-1β ratio of but not the individual cytokine levels. The

cytokine values of IL-1Ra and IL-1β were not influenced significantly, but a mild trend is present. Carriers of the G allele had a slightly lower BALF IL-1Ra level (P = 0·21) and a higher BALF IL-1β level (P = 0·16). Although both not significant, when the ratio is calculated this effect is enhanced. A hypothetical explanation is that the balance between pro- and anti-inflammatory cytokines is of more biological importance than the absolute concentrations of IL-1Ra

and IL-1β. Carter et al. [14] showed that carriage of the IL1RN + 2018 allele 2 was associated with a reduced colonic IL-1Ra protein level and a reduced IL-1Ra/total IL-1 ratio. It is likely that in our population a similar effect is present; very however, our population might not be big enough to illustrate this with significant results, and this should be replicated in a larger cohort. In conclusion, this study showed that variation in the IL1RN associates with susceptibility to IPF. The subsequent imbalance between IL-1β and IL-1Ra might have a significant pathogenetic effect in IPF patients. Better understanding of the role of these mediators in the context of disease susceptibility and progression is important, as it may help us to find rational for newly available therapies. The authors thank Annette van der Vis, Danielle Hijdra and Jan Broess for technical and laboratory assistance. None. “
“We previously showed alterations in the thymus during experimental infection with Plasmodium berghei. Such alterations comprised histological changes, with loss of cortical–medullary limits, and the intrathymic presence of parasites.