Do children's interstitial lung disease and idiopathic pulmonary fibrosis in adults share a common immunopathogenesis?
Abstract
Introduction: Idiopathic pulmonary fibrosis (IPF) is a severe lung disease characterized by a pathological pattern of healing of multiple alveolar lesions. An imbalance of regulatory, profibrotic and antifibrotic cytokines is very likely to play a role in the process.
Children's interstitial lung diseases (ILD) is a rare condition having a better prognosis than IPF in adults. In some cases, a common genetic background is assumed in children's ILDs and adult IPF such as surfactant protein gene mutation.
Little is known about genotypes of the cytokine genes which probably influence the pathogenetic pathways in the lungs in both diseases and about their potential common immunogenetic features. The aims of our study were to investigate cytokine gene polymorphisms in adult IPF and in children's ILDs and to compare them with each other and with healthy controls.
Material and methods: We investigated 56 adult patients with IPF and 19 patients with children's ILDs. The control group consisted of 145 healthy unrelated Caucasians.
Polymorphisms of the IL-lalpha, IL-lbeta, IL-IR, IL-IRA, lL-2, lL-4, IL-6, IL-10, IL-12, TNF-alpha, IFN-gamma, TGF-beta, IL-1 beta, IL-2, IL-4 and IL-4RA genes were characterized by the PCR-SSP method. Results: When comparing promotor gene polymorphisms of lL-4 in IPF and controls, significant differences were found at lL-4 (-590) and (-33) positions and in haplotype 1 IL-4 (-1 098) (-590) (-33).
As to the differences in polymorphism frequencies between children with ILDs and controls, we observed different frequencies of alleles in promotor regions of IL-1 beta (-511) and lL-10 (-819) and (-592) and also in haplotype 1 lL-10 (-1 082) (-819) (-592). No difference in polymorphisms was found between the IPF and children's ILDs groups.
Conclusion: The study supported our previous hypothesis about the role of cytokine gene polymorphisms in IPF pathogenesis, namely that of lL-4. The IL-4 promotor polymorphisms influence lL-4 production and thus could probably shift immune reactivity towards the so called Th2 type.
Sporadic children's ILDs probably do not share a common immunogenetic background with IPF in adults. If some cytokine gene polymorphisms take part in their pathogenesis, thanlhose of IL-IO, with low producer's phenotype.
Low IL-10 production could lead to immune reactivity shift towards the Th1 type with protective effects against uncontrolled fibropreduction, which could elucidate the better prognosis of children's ILDs.