Inflammatory Cytokine Response in Dengue Infected Female of Reproductive Age: Insight with Reference to a Pregnant Case

Authors

  • Ramanuj Rauniyar Central Department of Biotechnology, Institute of Science and Technology, Tribhuvan University, Kirtipur, Kathmandu, Nepal https://orcid.org/0000-0002-9672-2686
  • Binod Manandhar Department of Mathematical Science, Clark Atlanta University, Atlanta, Georgia, USA https://orcid.org/0000-0003-1522-0885
  • Satish Chandra Jha Central Department of Biotechnology, Institute of Science and Technology, Tribhuvan University, Kirtipur, Kathmandu, Nepal
  • Indu Bikram Joshi Central Department of Biotechnology, Institute of Science and Technology, Tribhuvan University, Kirtipur, Kathmandu, Nepal
  • Bimal Sharma Chalise Sukraraj Tropical & Infectious Disease Hospital, Teku, Kathmandu, Nepal
  • Paul K Wallace SciGro, Inc, WI, USA
  • William Telford NCI Laboratory of Pathology, MD, USA
  • Krishna Das Manandhar Central Department of Biotechnology, Institute of Science and Technology, Tribhuvan University, Kirtipur, Kathmandu, Nepal https://orcid.org/0000-0002-6798-4935

DOI:

https://doi.org/10.3126/jist.v29i2.65709

Keywords:

Dengue, inflammatory cytokines, pregnant, hematological, Flowcytometry

Abstract

Dengue treatment and management is challenging during the epidemic especially among the risk groups and to mitigate the risks becomes even more complicated in absence of specific medicine and vaccines. Till date, there are no specific research endeavours in Nepal focusing on pregnant women with dengue and there is evident gap in research concerning the treatment of pregnant women due to overlapping clinical and hematological manifestations with physiological changes of gestation. The study comprises clinically diagnosed one dengue positive pregnant female, five female patients with dengue in Sukraraj Tropical and Infectious Disease Hospital (STIDH), Kathmandu and five healthy volunteers of same reproductive age. The study investigates six different inflammatory cytokines; IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF levels in plasma and were quantified using Cytometric Bead Array. The Cytokine profiles and blood parameters were statistically analyzed using confidence intervals of 93.75% as permitted by sample size and visualized with box and whisker plot with a highlighted pregnant case. The study shows IL-6 and IL-10 levels are elevated on dengue cases as compared to healthy while TNF and IL-12p70 levels are elevated exceeding the upper limit of the acute dengue cases in the pregnant subject, underscoring heightened inflammatory activity during synchronous pregnancy and dengue infection. There were significant reductions in hemoglobin and leukocyte counts in the pregnant dengue case compared to non-pregnant. These findings suggest cytokine modulations occur during pregnancy and underscores the importance of these patterns provide insight into targeted therapeutic and diagnostic strategies to mitigate the risks for vulnerable population.

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References

Abu-Raya, B., Michalski, C., Sadarangani, M., & Lavoie, P.M. (2020). Maternal immunological adaptation during normal pregnancy. Frontiers in Immunology, 11, 575197. https://doi.org/10.3389/fimmu.2020.575197.

Bert, S., Ward, E.J., & Nadkarni, S. (2021). Neutrophils in pregnancy: New insights into innate and adaptive immune regulation. Immunology, 164(4), 665–676. https://doi.org/10.1111/imm.13392.

Bhattarai, B.R., Mishra, A., Aryal, S., Chhusyabaga, M., & Bhujel, R. (2023). Association of hematological and biochemical parameters with serological markers of acute dengue infection during the 2022 dengue outbreak in Nepal. Journal of Tropical Medicine, 2904422. https://doi.org/10.1155/2023/2904422.

Brat, D.J., Bellail, A.C., & Van Meir, E.G. (2005). The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro-Oncology, 7(2), 122-133.

Chen, L.C., Lei, H.Y., Liu, C.C., Shiesh, S.C., Chen, S.H., Liu, H.S., Lin, Y.S., Wang, S.T., Shyu, H.W., & Yeh, T.M. (2006). Correlation of serum levels of macrophage migration inhibitory factor with disease severity and clinical outcome in dengue patients. The American Journal of Tropical Medicine And Hygiene, 74(1), 142-147.

Cheng, S.B., & Sharma, S. (2015). Interleukin-10: a pleiotropic regulator in pregnancy. American Journal of Reproductive Immunology, 73(6), 487–500. https://doi.org/10.1111/aji.12329.

Cornish, E.F., Filipovic, I., Åsenius, F., Williams, D.J., & McDonnell, T. (2020). Innate immune responses to acute viral infection during pregnancy. Frontiers in Immunology, 11, 572567. https://doi.org/10.3389/fimmu.2020.572567.

EDCD. (2024). Dengue situation report. Epidemiology and Disease Control Division, Ministry of Health and Population, Government of Nepal. Retrieved December 26, 2024, from https://edcd.gov.np/news/20241007-dengue-situation-report.

Haider, S., & Knöfler, M. (2009). Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium. Placenta, 30(2), 111–123. https://doi.org/10.1016/j.placenta.2008.10.012.

Hober, D., Poli, L., Roblin, B., Gestas, P., Chungue, E., Granic, G., Imbert, P., Pecarere, J.L., Vergez-Pascal, R., Wattre, P., & Maniez-Montreuil, M. (1993). Serum Levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Interleukin-1β (IL-1β) in Dengue-Infected Patients. The American Journal of Tropical Medicine and Hygiene, 48(3), 324-331.

Horstick, O., Jaenisch, T., Martinez, E., Kroeger, A., See, L.L.C., Farrar, J., & Ranzinger, S.R. (2014). Comparing the usefulness of the 1997 and 2009 WHO dengue case classification: a systematic literature review. The American journal of tropical medicine and hygiene, 91(3), 621.

Kaur, G., Soni, S., Aggarwal, S., & Saini, A.S. (2014). Vertical Transmission of Dengue—A Case Report. Journal of Obstetrics and Gynecology of India, 64(1), 1–2. https://doi.org/10.1007/s13224-012-0253-6.

Kaur, P., & Kaur, G. (2014). Transfusion support in patients with dengue fever. International Journal of Applied and Basic Medical Research, 4(3), 8. https://doi.org/10.4103/2229-516x.140708.

Khanam, A., Gutiérrez-Barbosa, H., Lyke, K.E., & Chua, J.V. (2022). Immune-mediated pathogenesis in dengue virus infection. Viruses, 14(11), 2575. https://doi.org/10.3390/v14112575.

Lane, B.R., Liu, J., Bock, P.J., Schols, D., Coffey, M.J., Strieter, R.M., Polverini, P.J., & Markovitz, D.M. (2002). Interleukin-8 and growth-regulated oncogene alpha mediate angiogenesis in Kaposi's sarcoma. Journal of Virology, 76(22), 11570–11583. https://doi.org/10.1128/jvi.76.22.11570-11583.2002.

Malavige, G.N., Jeewandara, C., & Ogg, G.S. (2020). Dysfunctional Innate Immune Responses and Severe Dengue. Frontiers in cellular and infection microbiology. 10, 590004. https://doi.org/10.3389/fcimb.2020.590004.

Napit, R., Elong Ngono, A., Mihindukulasuriya, K.A., Pradhan, A., Khadka, B., Shrestha, S., Droit, L., Paredes, A., Karki, L., Khatiwada, R., Tamang, M., Chalise, B.S., Rawal, M., Jha, B.K., Wang, D., Handley, S.A., Shresta, S., & Manandhar, K.D. (2024). Dengue virus surveillance in Nepal yields the first on-site whole genome sequences of isolates from the 2022 outbreak. BMC Genomics, 25(1), 998. https://doi.org/10.1186/s12864-024-10879-x.

Paixao, E.S., Harron, K., Campbell, O., Teixeira, M.G., Costa, M.D.C.N., Barreto, M.L., & Rodrigues, L.C. (2018). Dengue in pregnancy and maternal mortality: A cohort analysis using routine data. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-28387-w.

Prins, J.R., Gomez-Lopez, N., & Robertson, S.A. (2012). Interleukin-6 in pregnancy and gestational disorders. Journal of Reproductive Immunology, 95(1-2), 1–14. https://doi.org/10.1016/j.jri.2012.05.004.

Rajapakse, S., de Silva, N.L., Weeratunga, P., Rodrigo, C., & Fernando, S.D. (2017). Prophylactic and therapeutic interventions for bleeding in dengue: A systematic review. Transactions of the Royal Society of Tropical Medicine and Hygiene, 111(10), 433–439. https://doi.org/10.1093/trstmh/trx079.

Rauniyar, R., Prajapati, S., Manandhar, B., Bastola, A., Chalise, B.S., Shrestha, S., Khanal, C., Thapa, M., Napit, R., Bajracharya, A.M., Shrestha, S., Adhikari, A., & Manandhar, K.D. (2023). Dengue virus infection during window period of consecutive outbreaks in Nepal and assessment of clinical parameters. Scientific Reports, 13(1), 9262. https://doi.org/10.1038/s41598-023-35928-5.

Rimal, S., Shrestha, S., Pandey, K., Nguyen, T.V., Bhandari, P., Shah, Y., Acharya, D., Adhikari, N., Rijal, K.R., Ghimire, P., Takamatsu, Y., Pandey, B.D., Fernandez, S., Morita, K., Ngwe Tun, M.M., & Dumre, S.P. (2023). Co-Circulation of Dengue Virus Serotypes 1, 2, and 3 during the 2022 Dengue Outbreak in Nepal: A Cross-Sectional Study. Viruses, 15(2), 507. https://doi.org/10.3390/v15020507.

Salazar Flórez, J.E., Marín Velasquez, K., Segura Cardona, Á.M., Restrepo Jaramillo, B.N., Ortega Díaz, Y.E., Giraldo Cardona, L. S., & Arboleda Naranjo, M. (2024). Clinical manifestations of dengue in children and adults in a hyperendemic region of Colombia. The American journal of tropical medicine and hygiene, 110(5), 971–978. https://doi.org/10.4269/ajtmh.23-0717.

Sharma, S., Jain, S., & Rajaram, S. (2016). Spectrum of Maternofetal Outcomes during Dengue Infection in Pregnancy: An Insight. Infectious Diseases in Obstetrics and Gynecology, 5046091. https://doi.org/10.1155/2016/5046091.

Simmons, C.P., Farrar, J. J., van Vinh Chau, N., & Wills, B. (2012). Dengue. The New England Journal of Medicine, 366(15), 1423–1432. https://doi.org/10.1056/nejmra1110265.

Tinsley, J.H., South, S., Chiasson, V.L., & Mitchell, B.M. (2010). Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure in hypertensive pregnant rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 298(3), R713–R719. https://doi.org/10.1152/ajpregu.00712.2009.

Villamor, E., Villar, L. A., Lozano, A., Herrera, V.M., & Herrán, O.F. (2017). Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome. Epidemiology and Infection, 145(14), 2961–2970. https://doi.org/10.1017/S0950268817002059.

Vilotić, A., Nacka-Aleksić, M., Pirković, A., Bojić-Trbojević, Ž., Dekanski, D., & Jovanović Krivokuća, M. (2022). IL-6 and IL-8: An Overview of Their Roles in Healthy and Pathological Pregnancies. International Journal of Molecular Sciences, 23(23), 14574. https://doi.org/10.3390/ijms232314574.

Wong, M.P., Juan, E.Y.W., Chelluri, S.S., Wang, P., Pahmeier, F., Castillo-Rojas, B., Blanc, S.F., Biering, S.B., Vance, R.E., & Harris, E. (2023). The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection. bioRxiv: the Preprint Server for Biology, https://doi.org/10.1101/2023.09.21.558875.

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Published

2024-12-31

How to Cite

Rauniyar, R., Manandhar, B., Jha, S. C., Joshi, I. B., Chalise, B. S., Wallace, P. K., … Manandhar, K. D. (2024). Inflammatory Cytokine Response in Dengue Infected Female of Reproductive Age: Insight with Reference to a Pregnant Case. Journal of Institute of Science and Technology, 29(2), 175–182. https://doi.org/10.3126/jist.v29i2.65709

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Research Articles