AIMS: 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.
AIMS: 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 sarcoidosiscytokine 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: Elliott D Crouser; Daniel A Culver; Kenneth S Knox; Mark W Julian; Guohong Shao; Susamma Abraham; Sandya Liyanarachchi; Jennifer E Macre; Mark D Wewers; Mikhail A Gavrilin; Patrick Ross; Abbas Abbas; Charis Eng Journal: Am J Respir Crit Care Med Date: 2009-02-12 Impact factor: 21.405
Authors: M Heron; J C Grutters; C H M van Moorsel; H J T Ruven; T W J Huizinga; A H M van der Helm-van Mil; A M E Claessen; J M M van den Bosch Journal: Genes Immun Date: 2009-07-23 Impact factor: 2.676
Authors: Michiel Heron; Jan C Grutters; Heleen van Velzen-Blad; Marcel Veltkamp; Anke M E Claessen; Jules M M van den Bosch Journal: Chest Date: 2008-07-18 Impact factor: 9.410
Authors: Marc A Judson; Robert P Baughman; Bruce W Thompson; Alvin S Teirstein; Michael L Terrin; Milton D Rossman; Henry Yeager; Geoffrey McLennan; Eddy A Bresnitz; Louis DePalo; Gary Hunninghake; Michael C Iannuzzi; Carol J Johns; David R Moller; Lee S Newman; David L Rabin; Cecile Rose; Benjamin A Rybicki; Steven E Weinberger; Genell L Knatterud; Reuben Cherniak Journal: Sarcoidosis Vasc Diffuse Lung Dis Date: 2003-10 Impact factor: 0.670
Authors: Annegret Fischer; David Ellinghaus; Marcel Nutsua; Sylvia Hofmann; Courtney G Montgomery; Michael C Iannuzzi; Benjamin A Rybicki; Martin Petrek; Frantisek Mrazek; Stefan Pabst; Christian Grohé; Johan Grunewald; Marcus Ronninger; Anders Eklund; Leonid Padyukov; Violeta Mihailovic-Vucinic; Dragana Jovanovic; Martina Sterclova; Jiri Homolka; Markus M Nöthen; Stefan Herms; Christian Gieger; Konstantin Strauch; Juliane Winkelmann; Bernhard O Boehm; Stephan Brand; Carsten Büning; Manfred Schürmann; Eva Ellinghaus; Hansjörg Baurecht; Wolfgang Lieb; Almut Nebel; Joachim Müller-Quernheim; Andre Franke; Stefan Schreiber Journal: Am J Respir Crit Care Med Date: 2015-09-15 Impact factor: 21.405