title: Circulating cytokines in sarcoidosis: phenotype-specific alterations for fibrotic and non-fibrotic pulmonary disease.
abstract: OBJECTIVE
  Sarcoidosis is a granulomatous disease of unknown etiology marked by tremendous clinical heterogeneity. Many patients enter remission with good long-term outcomes. Yet, chronic disease is not uncommon, and this important phenotype remains understudied. Identified alterations in local and circulating cytokines--specifically targeted for study, and often in the acute phase of disease--have informed our growing understanding of the immunopathogenesis of sarcoidosis. Our aim was to evaluate a broad panel of circulating cytokines in patients with chronic sarcoidosis. Among those with chronic disease, pulmonary fibrosis occurs in only a subset. To gain more insight into the determinants of the fibrotic response, we also determined if the phenotypes of fibrotic and non-fibrotic pulmonary sarcoidosis have distinct cytokine profiles.
  
  
  RESULTS
  In patients with sarcoidosis compared to controls, IL-5 was decreased, and IL-7 was increased. Both of these comparisons withstood rigorous statistical correction for multiple comparisons. GM-CSF met a nominal level of significance. We also detected an effect of phenotype, where IL-5 was significantly decreased in non-fibrotic compared to fibrotic pulmonary sarcoidosis, and compared to controls. Compared to controls, there was a trend towards a significant increase in IL-7 in fibrotic, but not in non-fibrotic pulmonary sarcoidosis. In contrast, compared to controls, there was a trend towards a significant increase in GM-CSF in non-fibrotic, but not in fibrotic pulmonary sarcoidosis.
  
  
  CONCLUSIONS
  In a comprehensive evaluation of circulating cytokines in sarcoidosis, we found IL-5, IL-7, and GM-CSF to be altered. These findings provide a window into the immunopathogenesis of sarcoidosis. IL-7 is a novel sarcoidosis cytokine and, as a master regulator of lymphocytes, is an attractive target for further studies. By observing an effect of phenotype upon cytokine patterns, we also identify specific immune alterations which may contribute to clinical heterogeneity.
authors: Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL, United States. karen.patterson@uphs.upenn.edu
authors: Karen C
authors: KC
authors: Patterson
authors: Beverly S
authors: BS
authors: Franek
authors: Joachim
authors: J
authors: Müller-Quernheim
authors: Anne I
authors: AI
authors: Sperling
authors: Nadera J
authors: NJ
authors: Sweiss
authors: Timothy B
authors: TB
authors: Niewold
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D003710:Demography; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011658:Pulmonary Fibrosis / Q000097:blood* / Q000473:pathology*; D012507:Sarcoidosis / Q000097:blood* / Q000473:pathology*
chemical_list: D016207:Cytokines
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