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Expression of pro-inflammatory cytokines (IL-6 & IL-18) exacerbate the risk of diabetic nephropathy in the Pakistani population

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Abstract

Background

Diabetic nephropathy (DN) is a micro-chronic diabetic consequence induced by metabolic and hemodynamic abnormalities. Free radicals react with other critical cellular components, causing progression of aberrant renal function.

Objective

This case control study was aimed to determine the role of IL-6 and IL-18 in diabetic nephropathy in Pakistani population.

Methods and materials

The study's subjects (n = 180 from Lahore, Gujranwala, and Karachi) were divided into control, diabetes mellitus (DM) and diabetic nephropathy (DN) groups. The serum concentration of IL-6 & IL-18 were determined by enzyme-linked immunosorbent assay (ELISA). The expression analysis of IL-6 & IL-18 were performed by Real Time PCR.

Results

The significant increase in serum levels of IL-6 were observed among the control, DM and DN groups (15.3 ± 24.1 pg/ml, 34.7 ± 24.0 pg/ml, 52.6 ± 33.2 pg/ml) whereas no significant difference was observed in serum levels of IL-18. The expression analysis of IL-6 was increased by more than forty three fold in DN group (n-fold = ~43.6) as compared to DM & control whereas the expression profile of IL-18 decreased in DN group (n-fold = ~0.89). In DN group the correlation analysis revealed direct association of GFR with serum IL-6 (r = 0.1114) & inverse relationship with serum IL-18 (r = − 0.097). In multiple regression analysis using GFR as the dependent variable, BMI and expression of IL-18 were determinants in DM subjects, but only uric acid in DN subjects.

Conclusion

The present study implicates that increased expression of IL-6 and decreased of IL-18 was associated with development of DN in Pakistani population.

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Acknowledgements

We would like to express our deepest gratitude to the doctors of all hospitals that participated as well as the patients themselves for their invaluable assistance with the clinical evaluation and the collecting of blood samples. The authors appreciate Dr. Farhana Rasheed, Dr. Amaan and Dr. Nimra Yaseen for patient identification and blood sampling. We also appreciate Umair Rasheed's help in blood sampling and travel assistance.

Funding

This research was funding by Lahore College for Women University (LCWU), Lahore grant number by TR-158/6523.

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Authors and Affiliations

  1. Department of Zoology, Lahore College for Women University, Lahore, Pakistan

    Maha Maqsood, Saima Sharif, Shagufta Naz, Tasnim Farasat & Farkhanda Manzoor

  2. DHQ Teaching Hospital Gujranwala, Civil Lines, Gujranwala, Pakistan

    Maqsood Cheema

  3. THQ, Hospital, Muridke, Sheikhupura, Pakistan

    Muhammad Saqib

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  1. Maha Maqsood
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Contributions

MM: data and sample collection, research work, writing—original draft preparation, results analysis, editing, visualization; SS: supervision, conceptualization, methodology, manuscript review, statistical analysis; SN: methodology, data analysis, manuscript review; TF: supervision, data handling, manuscript review; FM: resources, manuscripit review and editing; MC: identification of patients and blood sampling, manuscript review; MS: identification of patients and help in blood sampling. data handling, manuscript review and approval. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Corresponding author

Correspondence to Saima Sharif.

Ethics declarations

Ethical approval

The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Ethical Review Committee of Lahore College for Women University, Lahore. (No. REF/NO/LCWU/ZOO/586-; Dated: 18-01-2019). We also received IRB approval letter from Shaikh Zayed Medical Complex, Lahore (IRB ID: SZMC/IRB/Internal/265/2020). We received permission letter of blood sampling from Civil Hospital. Karachi (REF NO: 12449; Date: 16-11-2020) and DHQ, Hospital for Gujranwala (Memo # 21; Date: 27-7-2020).

Consent to participate

Prior to their participation, all of the participants gave their informed consent, and the data were either pseudonymized or anonymized, depending on the circumstance.

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The authors state that they have no conflicts of interest.

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11033_2023_8249_MOESM1_ESM.docx

Supplementary file 1 (DOCX 22 KB)—Table S1: Demographic and Biochemical characteristics of Lahore, Gujranwala and Karachi population. Table S2: Correlation analysis of Serum IL-6, Serum IL-18, IL-6 Expression and IL-18 Expression with clinical risk factor in the control , diabetic and Diabetic nephropathy subjects of Lahore. Table S3: Correlation analysis of Serum IL-6, Serum IL-18, IL-6 Expression and IL-18 Expression with clinical risk factor in the control , diabetic and Diabetic nephropathy subjects of Gujranwala. Table S4: Correlation analysis of Serum IL-6, Serum IL-18, IL-6 Expression and IL-18 Expression with clinical risk factor in the control , diabetic and Diabetic nephropathy subjects of Karachi.

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Maqsood, M., Sharif, S., Naz, S. et al. Expression of pro-inflammatory cytokines (IL-6 & IL-18) exacerbate the risk of diabetic nephropathy in the Pakistani population. Mol Biol Rep 50, 3249–3257 (2023). https://doi.org/10.1007/s11033-023-08249-z

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