T-889C IL-1α promoter polymorphism influences the response to oral cyclophosphamide in scleroderma patients with alveolitis

Lorenzo Beretta, Francesca Cappiello, Morena Barili, Francesca Bertolotti, Raffaella Scorza

Research output: Contribution to journalArticlepeer-review


Cyclophosphamide (CYC) is the cornerstone of the treatment of systemic sclerosis (SSc)-associated fibrosing alveolitis (FAS). Despite treatment with CYC, in a not negligible proportion of SSc-FAS patients, deterioration in lung function can be observed. Interleukin-1 (IL-1) cluster gene single nucleotide polymorphisms (SNPs) were implicated in the pathogenesis of some interstitial lung diseases and may favor the progression of restrictive lung disease in SSc. The present retrospective case-control study was conducted on 18 SSc patients previously treated with oral CYC (2 mg/kg) and medium-dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day) for the presence of FAS - defined as the presence of areas of ground-glass attenuation on high-resolution computed tomography (HRCT) and a recent deterioration in lung function. The T/C substitution at position -889 of the IL-1 promoter gene (T-889C) was determined by polymerase chain reaction and restriction length fragment analysis. Patients carrying the T allele showed a significant decrease in forced vital capacity (FVC) values after 12 months of therapy (2.46±1.09 vs 2.59±1.17 l), while wild-type patients showed an increase in FVC values (2.73±0.54 vs 2.54±0.5 l) (p=0.005 between the two groups, analysis of variance for repeated measures). Patients with the T-889C polymorphism presented higher baseline erythrocyte sedimentation rates (ESR) compared to wild-type patients (50.3±25.4 vs 23.3±17.7 mm/h). Baseline ESR inversely correlated with the variation of FVC (ΔFVC) after 12 months of therapy (r=-0.50 and p

Original languageEnglish
Pages (from-to)88-91
Number of pages4
JournalClinical Rheumatology
Issue number1
Publication statusPublished - Jan 2007


  • Cyclophosphamide
  • Lung
  • Polymorphism
  • Systemic sclerosis

ASJC Scopus subject areas

  • Immunology
  • Rheumatology


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