Elevated Co-infection in Hepatitis C Virus and Toxoplasmosis Patients With IL-32, IL-33 and TNF-α
Amjad T. Hameed 1*, Nazar Sh. Mohammed 1, Amani M. Jasim 1
Journal of Angiotherapy 8(4) 1-9 https://doi.org/10.25163/angiotherapy.849566
Submitted: 04 March 2024 Revised: 03 April 2024 Published: 06 April 2024
Abstract
Background: Hepatitis C virus (HCV) infection is a major global health concern, often leading to chronic liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma. Toxoplasmosis, caused by Toxoplasma gondii, primarily affects the central nervous system but can also cause severe symptoms when co-infected with HCV, particularly in the liver. The relationship between these two infections and their impact on cytokine levels, especially interleukins (IL-32, IL-33) and tumor necrosis factor alpha (TNF-α), remains poorly understood. Methods: A case-control study was conducted involving 100 HCV-infected patients, 20 of whom were co-infected with both HCV and Toxoplasma. Blood samples were collected, and serological assays were performed to measure levels of HCV and Toxoplasma antibodies (IgM and IgG). Additionally, cytokine levels (IL-32, IL-33, TNF-α) were quantified using enzyme-linked immunosorbent assays (ELISA). DNA sequencing was performed to analyze gene variations associated with cytokine production. Results: Co-infected patients exhibited significantly higher levels of HCV and Toxoplasma antibodies compared to HCV-infected individuals without Toxoplasma co-infection (p < 0.001). Furthermore, levels of IL-32, IL-33, and TNF-α were elevated in co-infected patients, indicating a potential role of these cytokines in disease severity. The mean levels of IL-32, IL-33, and TNF-α were 10.110±0.596, 24.914±2.308, and 12.356±1.369, respectively, in co-infected patients. Conclusion: Co-infection with HCV and toxoplasmosis is associated with elevated levels of pro-inflammatory cytokines IL-32, IL-33, and TNF-α, suggesting a dysregulated immune response. These findings highlight the importance of understanding cytokine dynamics in co-infected patients for targeted therapeutic interventions and improved clinical management. DNA sequencing revealed variations in genes encoding cytokines, suggesting a genetic predisposition to elevated cytokine levels and disease progression.
Keywords: Hepatitis C Virus (HCV), Toxoplasmosis, Cytokine Levels, Interleukins (IL-32, IL-33), Tumor Necrosis Factor Alpha (TNF-α)
References
Akoolo, L., Rocha, S. C., & Parveen, N. (2022). Protozoan co-infections and parasite influence on the efficacy of vaccines against bacterial and viral pathogens. Frontiers in Microbiology, 13, 1020029. https://doi.org/10.3389/fmicb.2022.1020029
Al-Azzawi, K. G. R., Al-Naqeeb, A. A. A. G., & Zeidan, M. A. K. (2022). Impact of Chronic Liver Diseases on Specific Health-Related Quality of Life among a Sample in Babylon Governorate. Journal of Techniques, 4(33), 86-90. https://doi.org/10.51173/jt.v4i33.648
Alkhuder, K. (2023). Raman Scattering-Based Optical Sensing Of Chronic Liver Diseases. Photodiagnosis and Photodynamic Therapy, 46, 103505. https://doi.org/10.1016/j.pdpdt.2023.103505
Backmund, M., Reimer, J., Meyer, K., Gerlach, J. T., & Zachoval, R. (2005). Hepatitis C virus infection and injection drug users: prevention, risk factors, and treatment. Clinical Infectious Diseases, 40(Supplement_5),S330-S335. https://doi.org/10.1086/427475
Bazmjoo, A., Bagherzadeh, M. A., Raoofi, R., Taghipour, A., Mazaherifar, S., Sotoodeh, H., Ostadi, Z., Shadmand, E., Jahromi, M. A., & Abdoli, A. (2023). Toxoplasma gondii, HBV, and HCV co-infection and their correlation with CD4 cells among Iranian HIV-positive patients. Immunity, Inflammation and Disease, 11(2), e794. https://doi.org/10.1002/iid3.794
Bulut, O., Kilic, G., & Domínguez-Andrés, J. (2022). Immune memory in aging: a wide perspective covering microbiota, brain, metabolism, and epigenetics. Clinical Reviews in Allergy & Immunology, 63(3), 499-529. https://doi.org/10.1007/s12016-021-08905-x
Bunet, R., Roy-Cardinal, M. H., Ramani, H., Cleret-Buhot, A., Durand, M., Chartrand-Lefebvre, C., Routy, J. P., Thomas, R., Trottier, B., Ancuta, P., & Hanna, D. B. (2023). Differential Impact of IL-32 Isoforms on the Functions of Coronary Artery Endothelial Cells: A Potential Link with Arterial Stiffness and Atherosclerosis. Viruses, 15(3), 700. https://doi.org/10.3390/v15030700
Collister, M., Rempel, J., Yang, J., Kaita, K., Raizman, Z., Gong, Y., & Minuk, G. (2019). Circulating and inducible IL-32α in chronic hepatitis C virus infection. Canadian Liver Journal, 2(1), 23-30. https://doi.org/10.3138/canlivj.2018-0003
Collister, M., Rempel, J., Yang, J., Kaita, K., Raizman, Z., Gong, Y., Minuk, G. (2019). Circulating and inducible IL-32α in chronic hepatitis C virus infection. Canadian Liver Journal, 2(1), 23-30. https://doi:10.3138/canlivj.2018-0003
Dhefer, I. H. (2021). Liver damage during infections with coronavirus. Journal of Techniques, 3(2), 79-85. https://doi.org/10.51173/jt.v3i2.302
El-Nahas, H. A., El-Tantawy, N. L., Farag, R. E., & Alsalem, A. M. (2014). Toxoplasma gondii infection among chronic hepatitis C patients: a case-control study. Asian Pacific Journal of Tropical Medicine, 7, 589-593.
Fahey, S., Dempsey, E., & Long, A. (2014). The role of chemokines in acute and chronic hepatitis C infection. Cellular & Molecular Immunology, 11(1), 25-40. https:// doi:10.1038/cmi.2013.37
Greigert, V., Di Foggia, E., Filisetti, D., Villard, O., Pfaff, A. W., Sauer, A., & Candolfi, E. (2019). When biology supports clinical diagnosis: review of techniques to diagnose ocular toxoplasmosis. British Journal of Ophthalmology, 103(7), 1008-1012. https://doi:10.1136/bjophthalmol-2019-313884
Haider Iskandar Flayh, Al-Marsomy, Huda Dhaher, Khazaali, Enas Adnan Abdulrasol. (2024). TLR-4 Polymorphisms Shows The Genetic Susceptibility to Toxoplasmosis and Polycystic Ovary Syndrome, Journal of Angiotherapy, 8(4), 1-8, 9596.
Hunter, P. (2018). Co-infection: when whole can be greater than the sum: the complex reaction to co-infection of different pathogens can generate variable symptoms. EMBO Reports, 19(8), e46601.https: //doi:10.15252/embr.201846601
Ifijen, I. H., Atoe, B., Ekun, R. O., Ighodaro, A., & Odiachi, I. J. (2023). Treatments of Mycobacterium tuberculosis and Toxoplasma gondii with Selenium Nanoparticles. BioNanoScience, 13, 249-277. https://doi:10.1007/s12668-023-01059-4
Jia, Z., Guo, M., Ge, X., Chen, F., & Lei, P. (2023). IL-33/ST2 Axis: A Potential Therapeutic Target in Neurodegenerative Diseases. Biomolecules, 13(10), 1494. https: //doi:10.3390/biom13101494
Latini, A., De Benedittis, G., Colafrancesco, S., Perricone, C., Novelli, G., Novelli, L., Priori, R., Ciccacci, C., & Borgiani, P. (2023). PCSK3 Overexpression in Sjögren’s Syndrome Patients May Be Regulated by rs4932178 SNP in Its Promoter Region and Correlates with IFN-γ Gene Expression. Genes, 14(5), 981. https://doi:10.3390/genes14050981
Liang, Y., Ou, Q., Power, R., & Griffin, M. (2023). Revisiting regulatory T cells as modulators of innate immune response and. Frontiers in Immunology, 14, 1287465. https://doi:10.3389/fimmu.2023.1287465
Medina, L., Guerrero-Muñoz, J., Castillo, C., Liempi, A., Fernández-Moya, A., Araneda, S., Ortega, Y., Rivas, C., Maya, J. D., & Kemmerling, U. (2022). Differential microRNAs expression during ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii. Acta Tropica, 235, 106651..https:// doi:10.1016/j.actatropica.2022.106651
Metwally, M., El-Shanshory, M., Allam, N., Soliman, R., & Abu Ouf, H. (2021). A study on some factors affecting CMV reactivation in allogeneic hematopoietic stem cells transplantation. International Journal of Cancer and Biomedical Research, 5(3), 165-175. https://doi:10.21608/JCBR.2020.50141.1095
Murdaca, G., Paladin, F., Tonacci, A., Borro, M., Greco, M., Gerosa, A., Isola, S., Allegra, A., & Gangemi, S. (2022). Involvement of Il-33 in the pathogenesis and prognosis of major respiratory viral infections: Future perspectives for personalized therapy. Biomedicines, 10(3), 715.https: //doi:10.3390/biomedicines10030715
Naranje, P., Bhalla, A. S., Jana, M., Garg, M., Nair, A. D., Singh, S. K., & Banday, I. (2022). Imaging of pulmonary superinfections and co-infections in COVID-19. Current Problems in Diagnostic Radiology, 51(5), 768-778.
Parsaeimehr, A., & Ozbay, G. (2023). Utilizing HRPzyme, a cost-effective Vibrio parahaemolyticus detection method. LWT, 189, 115461. https://doi:10.1016/j.lwt.2023.115461
Rasheed, N. F. A., Jassim, H. S., & Hassan, A. S. (2022). Assessment of Some Heavy Metals and Trace Elements in a Sample of Patients with Viral Hepatitis in Baghdad. Journal of Techniques, 4(3), 8.
Sana, M., Rashid, M., Rashid, I., Akbar, H., Gomez-Marin, J. E., & Dimier-Poisson, I. (2022). Immune response against toxoplasmosis—Some recent updates RH: Toxoplasma gondii immune response. International Journal of Immunopathology and Pharmacology, 36, 03946320221078436. https://doi.org/10.1177/03946320221078436
Schilcher, K., Dayoub, R., Kubitza, M., Riepl, J., Klein, K., Buechler, C., Melter, M., & Weiss, T. S. (2023). Saturated Fat-Mediated Upregulation of IL-32 and CCL20 in Hepatocytes Contributes to Higher Expression of These Fibrosis-Driving Molecules in MASLD. International Journal of Molecular Sciences, 24(17), 13222. https://doi.org/10.3390/ijms241713222
Sehree, M. M., Al-Kaysi, A. M., & Abdullah, H. N. (2023). A Developed Colorimetric Assay Using Unmodified Gold Nanoparticles for the Identification of Acinetobacter baumannii Isolates from Different Clinical Samples. Baghdad Science Journal. https://doi.org/10.21123/bsj.2023.6842.
Si, Y., Zhang, J., Bao, S., Wise, S. G., Wang, Y., Zhang, Y., & Tang, Y. (2022). IL-32 and IL-34 in hepatocellular carcinoma. Frontiers in Medicine, 9, 1051113. https://doi.org/10.3389/fmed.2022.1051113.
Tse, O. O., Jiang, P., Cheng, S. H., Peng, W., Shang, H., Wong, J., ... & Lo, Y. D. (2021). Genome-wide detection of cytosine methylation by single molecule real-time sequencing. Proceedings of the National Academy of Sciences, 118(5), e2019768118.. https://doi.org /10.1073/pnas.2019768118
Yang, L., Xie, X., Tu, Z., Fu, J., Xu, D., & Zhou, Y. (2021). The signal pathways and treatment of cytokine storm in COVID-19. Signal transduction and targeted therapy, 6(1), 255.doi.org/10.1038/s41392-021-00679-0
Yang, Q., Guo, N., Zhou, Y., Chen, J., Wei, Q., & Han, M. (2020). The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharmaceutica Sinica B, 10(11), 2156-2170. https://doi.org/10.1016/j.apsb.2020.04.004.
Yang, X., Su, B., Liu, J., Zheng, L., Tao, P., Lin, Y., Zou, X., Yang, H., Wu, W., Meng, P., & Zhang, T. (2023). A CpG-Oligodeoxynucleotide Suppresses Th2/Th17 Inflammation by Inhibiting IL-33/ST2 Signaling in Mice from a Model of Adoptive Dendritic Cell Transfer of Smoke-Induced Asthma. International Journal of Molecular Sciences, 24(4), 3130. https://doi.org/10.3390/ijms24043130.
Zaidan, S. (2019). Exploring the role of IL-32 in premature age-related cardiovascular diseases in HIV-infected individuals.
Zhang, X., Xu, J., Peng, H., et al. (2008). HCV coinfection associated with slower disease progression in HIV-infected former plasma donors naïve to ART. PLOS One, 3, e3992. https://doi.org/10.1111/ajt.15415.
Zheng, M., Li, J., Fang, W., Luo, L., Ding, R., Zeng, H., Luo, H., Lin, X., & Duan, C. (2023). The TNF-α rs361525 and IFN-γ rs2430561 polymorphisms are associated with liver cirrhosis risk: a comprehensive meta-analysis. Frontiers in Immunology, 14, 1129767. https://doi.org/10.3389/fimmu.2023.1129767.
View Dimensions
View Altmetric
Save
Citation
View
Share