Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-10-26

AUTHORS

Yuichi Ishikawa, Shigeru Iwata, Kentaro Hanami, Aya Nawata, Mingzeng Zhang, Kaoru Yamagata, Shintaro Hirata, Kei Sakata, Yasuyuki Todoroki, Kazuhisa Nakano, Shingo Nakayamada, Minoru Satoh, Yoshiya Tanaka

ABSTRACT

BackgroundDermatomyositis (DM) with rapidly progressive interstitial lung disease (DM RP-ILD) is a life-threatening condition. Serum cytokine levels are potentially suitable biomarkers for DM RP-ILD. However, the relationships among cytokine levels, lung imaging findings, and lung pathology have not been investigated. The aim of the present retrospective study was to determine the association between hypercytokinemia and lung inflammation in patients with DM RP-ILD.MethodsThe study subjects were nine patients with life-threatening DM RP-ILD and severe hypoxemia (partial arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio ≤ 200) before receiving intensive care management, who were admitted to our hospital between 2006 and 2015. The controls included 10 patients with DM without RP-ILD and 19 healthy subjects. We assessed the association between serum cytokine levels and computed tomography (CT) scores of the lung (ground glass opacity-score, G-score; fibrosis-score, F-score). Lung, hilar lymph nodes, and spleen from two autopsies were examined by hematoxylin-eosin (H&E) staining and immunostaining.ResultsSerum interferon (IFN)-γ, interleukin (IL)-1β and IL-12 levels were significantly higher in patients with DM RP-ILD than in the other two groups, whereas serum IL-6 levels were elevated in the two patient groups but not in the healthy subjects. Serum levels of IL-2, IL-4, IL-8, IL-10, IFN-α, and TNF (tumor necrosis factor)-α were not characteristically elevated in the DM RP-ILD group. Serum IFN-γ levels correlated with G-scores in patients with DM RP-ILD, while IL-1β was negatively correlation with F-scores. Immunohistochemical staining showed infiltration of numerous IFN-γ-positive histiocytes in the lung and hilar lymph nodes; but not in the spleen. Serum IL-6 levels did not correlate with the CT scores. Numerous IL-6-positive plasma cells were found in hilar lymph nodes, but not in the lungs or spleen.ConclusionsOur results suggest strong IFN-γ-related immune reaction in the lungs and hilar lymph nodes of patients with life-threatening DM RP-ILD, and potential IFN-γ involvement in the pathogenesis of DM, specifically in the pulmonary lesions of RP-ILD. More... »

PAGES

240

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13075-018-1737-2

DOI

http://dx.doi.org/10.1186/s13075-018-1737-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107867574

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30367666


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22 schema:description BackgroundDermatomyositis (DM) with rapidly progressive interstitial lung disease (DM RP-ILD) is a life-threatening condition. Serum cytokine levels are potentially suitable biomarkers for DM RP-ILD. However, the relationships among cytokine levels, lung imaging findings, and lung pathology have not been investigated. The aim of the present retrospective study was to determine the association between hypercytokinemia and lung inflammation in patients with DM RP-ILD.MethodsThe study subjects were nine patients with life-threatening DM RP-ILD and severe hypoxemia (partial arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2) ratio ≤ 200) before receiving intensive care management, who were admitted to our hospital between 2006 and 2015. The controls included 10 patients with DM without RP-ILD and 19 healthy subjects. We assessed the association between serum cytokine levels and computed tomography (CT) scores of the lung (ground glass opacity-score, G-score; fibrosis-score, F-score). Lung, hilar lymph nodes, and spleen from two autopsies were examined by hematoxylin-eosin (H&E) staining and immunostaining.ResultsSerum interferon (IFN)-γ, interleukin (IL)-1β and IL-12 levels were significantly higher in patients with DM RP-ILD than in the other two groups, whereas serum IL-6 levels were elevated in the two patient groups but not in the healthy subjects. Serum levels of IL-2, IL-4, IL-8, IL-10, IFN-α, and TNF (tumor necrosis factor)-α were not characteristically elevated in the DM RP-ILD group. Serum IFN-γ levels correlated with G-scores in patients with DM RP-ILD, while IL-1β was negatively correlation with F-scores. Immunohistochemical staining showed infiltration of numerous IFN-γ-positive histiocytes in the lung and hilar lymph nodes; but not in the spleen. Serum IL-6 levels did not correlate with the CT scores. Numerous IL-6-positive plasma cells were found in hilar lymph nodes, but not in the lungs or spleen.ConclusionsOur results suggest strong IFN-γ-related immune reaction in the lungs and hilar lymph nodes of patients with life-threatening DM RP-ILD, and potential IFN-γ involvement in the pathogenesis of DM, specifically in the pulmonary lesions of RP-ILD.
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29 ConclusionsOur results
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31 F-score
32 G score
33 IFN
34 IFN-γ levels
35 IL-10
36 IL-12 levels
37 IL-1β
38 IL-2
39 IL-4
40 IL-6 levels
41 IL-8
42 MethodsThe study subjects
43 RP-ILD
44 TNF
45 Tomography Score
46 aim
47 association
48 autopsies
49 biomarkers
50 care management
51 cells
52 conditions
53 control
54 correlation
55 cytokine levels
56 dermatomyositis
57 disease
58 findings
59 group
60 healthy subjects
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83 lymph nodes
84 management
85 necrosis
86 nodes
87 numerous IFN
88 pathogenesis
89 pathogenesis of DM
90 pathology
91 patient group
92 patients
93 plasma cells
94 positive histiocytes
95 present retrospective study
96 progressive interstitial lung disease
97 pulmonary lesions
98 reaction
99 relationship
100 relevance
101 results
102 retrospective study
103 scores
104 serum IFN-γ levels
105 serum IL-6 levels
106 serum cytokine levels
107 serum levels
108 severe hypoxemia
109 spleen
110 staining
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112 study
113 study subjects
114 subjects
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