CORRELATION OF INFLAMMATORY CYTOKINE INTERLEUKINE (IL-4) AND MATRIX-METALLOPROTEINASE-9 IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) presents with respiratory symptoms caused by airflow obstruction. Parenchymal abnormalities, constricted airway and inflammation are major causative factors associated with COPD. Proteases such as matrix metalloproteinases (MMP) and a pleiotropic cytokine Interleukin-4 (IL-4) play an important role in lung tissue remodeling. However, there is a dearth in studies correlating the levels of MMP9 and IL-4 in patients of COPD. This study aims to evaluate the serum levels of MMP-9 and IL-4 in COPD and correlate with clinical characteristics of COPD patients. Materials and methods: This case control study pre-screened 134 participants of which 40 were healthy and 94 were COPD patients from the Department of Pulmonary Medicine at the Prasad Institute of Medical Sciences Lucknow. Results: Significantly increased level of Serum MMP-9 (212.6 ± 75.5 ng/ml) were detected in COPD group as compared to the control group (97.5± 45.6 ng/ml). Also, the IL-4 levels were significantly different in the control group Conclusions: Detection of higher levels of MMP9 and IL-4 in patients suffering from COPD in the present study implies that these biomarkers could serve as markers for understanding the depth of COPD development and therapy.


INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is characterised by persistent respiratory symptoms and restricted airflow.Shortness of breath and a cough that may or may not produce mucus are the prominent symptoms [1].As COPD progresses, simple tasks like dressing or walking become more challenging.
[2] Although COPD cannot be cured, it can be prevented and treated.Airflow blockage, a characteristic of COPD, a diverse lung disorder, is not entirely reversible.The main causes of airflow restriction in COPD are thought to be structural abnormalities in the lung parenchyma, tiny airways, and inflammation [3].
Smoking, which is a major contributor to COPD, is a risk factor for the disease.In addition to genetics, environmental variables can have an impact on COPD.(4) In COPD lung tissue remodelling, the extracellular matrix renewal is known to be regulated by a class of proteases called matrix

MATERIALS AND METHODS
We have 134 participants that were prescreened for this case-control study, wherein percentage is between 50 -79 %; for GOLD-3, the predicted FEV1 percentage is 30 -49 %; and for GOLD-4, the predicted FEV1 percentage is less than 30 %.
To the best of our knowledge, this is the first study, in which serum MMP-9 has been analysed and also proved to be increased in a

Inflammatory cytokines
The result showed that the IL-4 levels were to enrolment, all participants were provided written information and their consent was taken.The study's methodology was approved by the University Ethical Committee of Subharti University, Meerut, where the study was registered.The inclusion criteria for COPD patients and Controls were as follows COPD -Age 40 -75 years and Patient who has symptoms of a persistent cough, sputum production, or dyspnea, and/or a history of exposure to risk factors for the disease.Controls -Healthy volunteers who will be non-COPD based on their medical-history, clinical examination Non-tobacco users, non-occupational exposure Severity Grading of COPD Patients who had a persistent cough, dyspnoea, a history of exposure to COPD risk factors, a forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio of less than 0.7, and reversibility by inhaled bronchodilators in FEV1 of less than 12 percent or 200 mL after two puffs of 200 mg salbutamol administered with a pressure metered-dose inhaler with spacer were considered to have COPD.GOLD guidelines [10] were used to establish the diagnostic criteria for COPD.For GOLD-1, the predicted FEV1 percentage is ≥ 80 %; for GOLD-2, the predicted FEV1 levels of MMP 9 and IL-4 increased significantly as the grading increased from 1 to 4. ( p=0.001)The level of IL-4 positively correlated with FEV1/FVC (r=.217 ,p= 0.036) and those of MMP 9 also positively correlated with FEV1/FVC (r=.252 ,p= 0.014).(Fig. 2) DISCUSSION In this population-based study, COPD patients had significantly higher serum MMP-9 and IL 4 compared to the healthy control subjects.MMP-9 may play a fundamental role in the aetiology of COPD.According to a prior study, MMP-9 was adversely linked with the degree of airway blockage (11).A population-based COPD cohort study found a correlation between MMP-9 and productive cough and decreased FEV1 (forced expiratory volume in first sec ).Furthermore, the burden of tobacco smoking exposure, assessed as number of pack years, was associated with increasing MMP-9/TIMP-1-ratio in both COPD and non-COPD, indicating Table 1 .Demographical and Clinical characteristics of the COPD population.

Figure 1 .
Figure 1.Correlations between plasma inflammatory cytokine levels and MMP-9 and pulmonary function indexes

Figure 2 .
Figure 2. Correlations between plasma inflammatory cytokine levels (IL4) and MMP-9 and pulmonary function indexes significantly different in the control group.As a pleiotropic cytokine, IL-4 plays a crucial role in type 2 T-helper responses and isotype class switching of B cells to IgE synthesis, and it has thus been suggested that IL-4 may have an important role in COPD pathogenesis [16,17] Serum MMP-9 and IL-4 expression rose in the current experiment, and this trend was similar with GOLD grade.All of these markers have a favourable correlation with COPD patients.These findings indicate that MMP-9, and IL 4 are closely related to the pathogenesis of inflammation and airflow limitation in the progression of COPD.CONCLUSION Patients with COPD had higher serum levels of MMP-9 and IL 4. With the GOLD Grading the elevated levels of MMP-9, IL 4 were discovered, demonstrating the correlation between these biomarkers and the severity of airway limitation in COPD.These findings imply that they could serve as markers for understanding the depth of COPD development and therapy.REFERENCES 1. Global Strategy for Prevention, Diagnosis and Management of COPD: 2021 Report (PDF).Global Initiative for Chronic Obstructive Lung Disease.25 November 2020.Retrieved 28 June 2021.2. Global Strategy for Prevention, Diagnosis and Management of COPD: 2021 Report (PDF).Global Initiative for Chronic Obstructive Lung Disease.25 November 2020.Retrieved 28 June 2021.