Seema Singh1, S K Verma2, Santosh Kumar1, M K Ahmad3, Anuradha Nischal4, S K Singh5, R K Dixit4. 1. Department of Respiratory Medicine, King George Medical University, Lucknow, Uttar Pradesh, 226003, India. 2. Department of Respiratory Medicine, King George Medical University, Lucknow, Uttar Pradesh, 226003, India. Electronic address: drskverma@rediffmail.com. 3. Department of Biochemistry, King George Medical University, Lucknow, Uttar Pradesh, 226003, India. 4. Department of Pharmacology & Therapeutics, King George Medical University, Lucknow, Uttar Pradesh, 226003, India. 5. Department of Community Medicine and Public Health, King George Medical University, Lucknow, Uttar Pradesh, 226003, India.
Abstract
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a non-specific inflammation, which involves the airways, lung parenchyma and pulmonary vessels. The inflammation causes the activation of inflammatory cells and the release of various inflammatory mediators such as interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha (TNF-a). The present study was designed to assess the serum cytokines [Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α)] levels in chronic obstructive pulmonary disease (COPD) patients and they were correlated with severity of disease by spirometric measurements. MATERIALS AND METHODS: A total of 384 COPD patients and 50 healthy controls were enrolled in this study. The COPD patients were divided according to gold stages ie: mild, moderate, severe and very severe. 5 ml of venous blood samples were taken from all participants and it was collected in a test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 min. Serum was separated and used to measure the amount of TNF-alpha, il-1beta, and IL-6. Spirometry was performed according to the criteria set by the Gold 2012 RESULTS: Tnf-α (pg/ml), IL-6 (pg/ml), IL-1β (pg/ml) serum levels in COPD patients and healthy controls subjects were measured. Tnf-α and IL-6 serum levels were significantly (<0.001) higher in COPD patients compared to healthy control subjects. Likewise, IL-1 beta levels were also significantly (p-value = 0.022) higher in COPD patients compared to healthy control subjects. The distribution of Tnf-α, IL-6, IL-1β (pg/ml) serum levels in COPD patients in relation to GOLD grading. There was a significant (p < 0.001) difference in the level of TNF-α, IL-6 and IL-1β (pg/ml) among the severity of COPD. The posthoc analysis revealed that the TNF-α was significantly (p < 0.05) higher among the than mild, moderate, severe and very severe COPD patients. A similar observation was also found for IL-6. However, IL-6 was significantly (p < 0.05) higher among mild, moderate, severe and very severe COPD patients. There was significant (p = < 0.0001) difference in the level of IL-1β in the different severity of COPD. The posthoc comparison test showed that IL-1β levels were significantly (p < 0.05) higher among the mild, moderate, severe and very severe COPD patients. CONCLUSION: The present study signifies that the levels of TNF-α, IL-1β, and IL-6 are directly proportional to the post-bronchodilator FEV1 percentage. Results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a non-specific inflammation, which involves the airways, lung parenchyma and pulmonary vessels. The inflammation causes the activation of inflammatory cells and the release of various inflammatory mediators such as interleukin-1 beta, interleukin-6 and tumor necrosis factor alpha (TNF-a). The present study was designed to assess the serum cytokines [Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α)] levels in chronic obstructive pulmonary disease (COPD) patients and they were correlated with severity of disease by spirometric measurements. MATERIALS AND METHODS: A total of 384 COPDpatients and 50 healthy controls were enrolled in this study. The COPDpatients were divided according to gold stages ie: mild, moderate, severe and very severe. 5 ml of venous blood samples were taken from all participants and it was collected in a test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 min. Serum was separated and used to measure the amount of TNF-alpha, il-1beta, and IL-6. Spirometry was performed according to the criteria set by the Gold 2012 RESULTS: Tnf-α (pg/ml), IL-6 (pg/ml), IL-1β (pg/ml) serum levels in COPDpatients and healthy controls subjects were measured. Tnf-α and IL-6 serum levels were significantly (<0.001) higher in COPDpatients compared to healthy control subjects. Likewise, IL-1 beta levels were also significantly (p-value = 0.022) higher in COPDpatients compared to healthy control subjects. The distribution of Tnf-α, IL-6, IL-1β (pg/ml) serum levels in COPDpatients in relation to GOLD grading. There was a significant (p < 0.001) difference in the level of TNF-α, IL-6 and IL-1β (pg/ml) among the severity of COPD. The posthoc analysis revealed that the TNF-α was significantly (p < 0.05) higher among the than mild, moderate, severe and very severe COPDpatients. A similar observation was also found for IL-6. However, IL-6 was significantly (p < 0.05) higher among mild, moderate, severe and very severe COPDpatients. There was significant (p = < 0.0001) difference in the level of IL-1β in the different severity of COPD. The posthoc comparison test showed that IL-1β levels were significantly (p < 0.05) higher among the mild, moderate, severe and very severe COPDpatients. CONCLUSION: The present study signifies that the levels of TNF-α, IL-1β, and IL-6 are directly proportional to the post-bronchodilator FEV1 percentage. Results provide population-based evidence that COPD is independently associated with low-grade systemic inflammation, with a different inflammatory pattern than that observed in healthy subjects. Overall, these results identify a novel systemic inflammatory COPD phenotype that may be the target of specific research and treatment.
Authors: Petar Ozretić; Miguel Inacio da Silva Filho; Calogerina Catalano; Irena Sokolović; Andrea Vukić-Dugac; Maja Šutić; Matea Kurtović; Gordana Bubanović; Sanja Popović-Grle; Sanda Skrinjarić-Cincar; Oliver Vugrek; Irena Jukić; Lada Rumora; Martina Bosnar; Miroslav Samaržija; Robert Bals; Marko Jakopović; Asta Försti; Jelena Knežević Journal: Genes (Basel) Date: 2019-10-09 Impact factor: 4.096