Role of cytokines produced by T helper immune-modulators in dengue pathogenesis: A systematic review and meta-analysis
Linh Tran, Institute of Fundamental and Applied Sciences, Duy Tan University, Ho Chi Minh City 700000, Vietnam; Faculty of Natural Sciences, Duy Tan University, Da Nang City 550000, Vietnam. Electronic address: trantthuylinh10@duytan.edu.vn.
Ibrahim Radwan, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: iradwan43@gmail.com.
Le Huu Minh, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; University of Medicine and Pharmacy at Ho Chi Minh, Ho Chi Minh City 700000, Vietnam. Electronic address: lehuunhatminh.md@ump.edu.vn.
Soon Khai Low, Department of Internal Medicine, Rochester General Hospital, NY
Mohammad Rashidul Hashan, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Bangladesh Civil Service, Ministry of Health and Family Welfare, Government of Bangladesh, Mohakhali, Dhaka, 1212, Bangladesh. Electronic address: hasandmck66@gmail.com.
Mohammad Diaa Gomaa, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Faculty of Pharmacy, Minia University, Minia, Egypt. Electronic address: mohammaddiaagomaa@gmail.com.
Mohamed Abdelmongy, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Faculty of Medicine, Misr University for Science and Technology, Al-Motamayez District, 6th of October City, Egypt. Electronic address: m.abdelmongy95@yahoo.com.
Abdullah I. Abdelaziz, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, 833 S. Wood St. MC 871, Chicago, IL, 60612, USA. Electronic address: abduaziz295@gmail.com.
Alaa Mohamed, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Faculty of Medicine, Alexandria University, Egypt. Electronic address: dr.alaakhaled93@gmail.com.
Gehad Mohamed Tawfik, Online Research Club (http://www.onlineresearchclub.org/), Nagasaki, Japan; Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: dr.gehadmohamed@hotmail.com.
Shusaku Mizukami, Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: mizukami@nagasaki-u.ac.jp.
Kenji Hirayama, Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: hiraken@nagasaki-u.ac.jp.
Nguyen Tien Huy, School of Tropical Medicine and Global Health (TMGH), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Electronic address: tienhuy@nagasaki-u.ac.jp.
Abstract
BACKGROUND AND OBJECTIVES: Modulation of the immune reaction is essential in the development of various diseases, including dengue's "Cytokine Tsunami", an increase in vascular permeability with concomitant severe vascular leakage. We aim to identify the role of T-helper (Th) cells, Th2 and Th7, with their related cytokines in dengue pathogenesis. MATERIAL AND METHODS: Nine electronic databases and manual search were applied to detect available publications. A meta-analysis using a fixed- or random-effect model was performed to measure standardized mean difference (SMD) with 95% confidence interval (CI). The National Institute of Health (NIH) tools for observational cohort, cross-sectional, and case-control studies were used to examine the risk of bias. The protocol was recorded in PROSPERO with CRD42017060230. RESULTS: A total of 38 articles were found including 19 case-control, 11 cross-sectional and 8 prospective cohort studies. We indicated that Th2 cytokines (IL-4, IL-6, IL-8) and Th17 cytokine (IL-17) in dengue patients were notably higher than in a healthy control group in acute phase (SMD = 1.59, 95% CI [0.68, 2.51], p = 0.001; SMD = 1.24, 95% CI [0.41, 2.06], p = 0.003; SMD = 1.13, 95% CI [0.61, 1.66], p<0.0001; SMD = 1.74, 95% CI [0.87, 2.61], p<0.0001), respectively. CONCLUSIONS: This study provides evidence of the significant roles of IL-4, IL-6, IL-8, IL-10 and IL-17 in the pathogenesis of developing a severe reaction in dengue fever. However, to fully determine the association of Th cytokines with dengue, it is necessary to perform further studies to assess kinetic levels during the duration of the illness.
