Malgorzata Jasiewicz1, Malgorzata Knapp2, Ewa Waszkiewicz3, Katarzyna Ptaszynska-Kopczynska4, Anna Szpakowicz5, Bozena Sobkowicz6, Wlodzimierz Jerzy Musial7, Karol Adam Kaminski8. 1. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: jasiewiczm@gmail.com. 2. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: malgo33@interia.pl. 3. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: ewawaszkiewicz@o2.pl. 4. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: kasia.ptaszynska@op.pl. 5. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: akodzi@poczta.onet.pl. 6. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: sobkowic@wp.pl. 7. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: musialwj@poczta.onet.pl. 8. Department of Cardiology, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24 A, 15-276 Bialystok, Poland. Electronic address: fizklin@wp.pl.
Abstract
BACKGROUND: The role of IL-6 in pulmonary arterial hypertension (PAH) has been reported but the prevalence of soluble receptors for IL-6: sIL-6R and sgp130 and its potential role in PAH have not been studied.Our aim was to examine the IL-6 together with the soluble receptors and to assess its relationship with clinical status of PAH patients as well as to assess its potential prognostic significance. METHODS: Serum concentrations of IL-6, sIL-6R and sgp130 were quantified by ELISA in 26 patients with PAH and 27 healthy controls and related to functional and biochemical parameters and clinical outcome in PAH group. The PAH patients were followed up for 1 year, noting the end point of clinical deterioration (WHO class change, the need for escalation of therapy) or death. RESULTS: The PAH group was characterized by higher median serum IL-6 [2.38 (IQR 1.56-3.75) vs 0.87 (0.63-1.3) pg/ml, p=0.000003] and sIL-6R concentrations [69.7 (IQR 60.4-84.4 vs 45.7 (34.6-70.3) ng/ml, p=0.0036] compared to control subjects. Both groups did not differ in sgp130 concentrations. There were significant correlations in PAH group between IL-6 levels and uric acid, parameters of ventilatory efficiency in cardiopulmonary exercise testing: VE/VO2, VE/VCO2, VE/VCO2 slope and peak PetCO2. sIL-6R levels inversely correlated with LDL cholesterol. After 1 year the clinical deterioration occurred in 11 patients, 15 remained stable. Patients in whom the clinical deterioration occurred showed significantly higher baseline concentrations of IL-6 [3.25 (IQR 2.46-5.4) pg/ml vs 1.68 (1.38-2.78) pg/ml, p=0.004], but not sIL-6R. Median IL-6 ⩾ 2.3 pg/ml (91% sensitivity, 73% specificity) identified subjects with worse clinical course. In the univariate analysis, higher IL-6 level at baseline was associated with increased risk and earlier occurrence of clinical deterioration (HR 1.42, 95%CI 1.08-1.85, p=0.015). CONCLUSIONS: IL-6 trans-signaling is enhanced in PAH. Elevated concentration of sIL-6R suggests its potential unfavorable role in systemic amplification of IL-6 signaling in PAH. Levels of IL-6 are associated with clinical indicators of disease severity as well as indirectly with systemic metabolic alterations. IL-6 shows prognostic value regarding predicting clinical deterioration.
BACKGROUND: The role of IL-6 in pulmonary arterial hypertension (PAH) has been reported but the prevalence of soluble receptors for IL-6: sIL-6R and sgp130 and its potential role in PAH have not been studied.Our aim was to examine the IL-6 together with the soluble receptors and to assess its relationship with clinical status of PAH patients as well as to assess its potential prognostic significance. METHODS: Serum concentrations of IL-6, sIL-6R and sgp130 were quantified by ELISA in 26 patients with PAH and 27 healthy controls and related to functional and biochemical parameters and clinical outcome in PAH group. The PAH patients were followed up for 1 year, noting the end point of clinical deterioration (WHO class change, the need for escalation of therapy) or death. RESULTS: The PAH group was characterized by higher median serum IL-6 [2.38 (IQR 1.56-3.75) vs 0.87 (0.63-1.3) pg/ml, p=0.000003] and sIL-6R concentrations [69.7 (IQR 60.4-84.4 vs 45.7 (34.6-70.3) ng/ml, p=0.0036] compared to control subjects. Both groups did not differ in sgp130 concentrations. There were significant correlations in PAH group between IL-6 levels and uric acid, parameters of ventilatory efficiency in cardiopulmonary exercise testing: VE/VO2, VE/VCO2, VE/VCO2 slope and peak PetCO2. sIL-6R levels inversely correlated with LDL cholesterol. After 1 year the clinical deterioration occurred in 11 patients, 15 remained stable. Patients in whom the clinical deterioration occurred showed significantly higher baseline concentrations of IL-6 [3.25 (IQR 2.46-5.4) pg/ml vs 1.68 (1.38-2.78) pg/ml, p=0.004], but not sIL-6R. Median IL-6 ⩾ 2.3 pg/ml (91% sensitivity, 73% specificity) identified subjects with worse clinical course. In the univariate analysis, higher IL-6 level at baseline was associated with increased risk and earlier occurrence of clinical deterioration (HR 1.42, 95%CI 1.08-1.85, p=0.015). CONCLUSIONS:IL-6 trans-signaling is enhanced in PAH. Elevated concentration of sIL-6R suggests its potential unfavorable role in systemic amplification of IL-6 signaling in PAH. Levels of IL-6 are associated with clinical indicators of disease severity as well as indirectly with systemic metabolic alterations. IL-6 shows prognostic value regarding predicting clinical deterioration.
Authors: Jenny Y Chen; Megan Griffiths; Jun Yang; Melanie K Nies; Rachel L Damico; Catherine E Simpson; R Dhananjay Vaidya; Stephanie Brandal; D Dunbar Ivy; Eric D Austin; William C Nichols; Michael W Pauciulo; Katie Lutz; Erika B Rosenzweig; Russel Hirsch; Delphine Yung; Allen D Everett Journal: J Pediatr Date: 2020-08 Impact factor: 4.406
Authors: Claudia Mickael; Rahul Kumar; Daniel Hernandez-Saavedra; Biruk Kassa; Linda Sanders; Dan Koyanagi; Sue Gu; Michael H Lee; Rubin M Tuder; Brian B Graham Journal: Am J Respir Cell Mol Biol Date: 2019-07 Impact factor: 6.914
Authors: Catherine E Simpson; Jenny Y Chen; Rachel L Damico; Paul M Hassoun; Lisa J Martin; Jun Yang; Melanie Nies; Megan Griffiths; R Dhananjay Vaidya; Stephanie Brandal; Michael W Pauciulo; Katie A Lutz; Anna W Coleman; Eric D Austin; Dunbar D Ivy; William C Nichols; Allen D Everett Journal: Eur Respir J Date: 2020-04-16 Impact factor: 16.671