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Cytokine receptors and fibroblast proliferation in interstitial pneumonia
  1. O C Ioachimescu
  1. Cleveland Clinic Foundation, Cleveland, USA; oioacyahoo.com

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Fibroblasts play a pivotal role in the pathogenesis of idiopathic interstitial pneumonia (IIP). Interleukin (IL)-4 and IL-13 are Th2-type profibrotic cytokines that exert their effects on fibroblasts via multimeric receptors comprised of several shared subunits: IL-4Rα, IL-13Rα1, IL-13Rα2, and γ. This study examined the differential expression of IL-4 and IL-13 receptors on cultured human fibroblasts from surgical lung biopsies of patients with different subtypes of IIP.

The fibroblasts from patients with usual interstitial pneumonia (UIP) had the highest gene and protein expression of the IL-4 specific type I receptor, IL-4 and IL-13 binding type 2 receptor, and a decoy receptor containing IL-13Rα2. A chimeric fusion protein comprised of IL-13 and Pseudomonas exotoxin A (IL-13PE), previously used to target IL-13-expressing malignant and inflammatory cells, markedly inhibited fibroblast proliferation, especially in cultures from patients with UIP. IL-13PE mediated effects on IIP fibroblasts seem to be via both IL-4Rα and IL-13Rα2, a finding that could potentially open new therapeutic avenues.

It would be interesting to see such results reproduced in a larger series of UIP, perhaps with the use of newer culture techniques such as laser capture microdissection. In addition, the confounding effect of fibroblast apoptosis in the process needs to be clarified and the findings confirmed by in vivo models. Finally, the extent to which a temporally and geographically heterogenous disease such as UIP follows an IL-4/IL-13 pathogenetic pathway, the homogeneity of the (myo)fibroblast population in IIP, and the role of IL-13PE or similar compounds in modulating fibroblast activity are all (as yet) unanswered questions.

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