A systematic review and meta-analysis of blood interleukin-4 levels concerning malaria infection and severity

• Published in: Malaria Journal
• Main Authors: Kwuntida Uthaisar Kotepui, Phiman Thirarattanasunthon, Pongruj Rattaprasert, Manas Kotepui
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2022
• Subjects: Severe malaria; Interleukin-4; IL-4; Cerebral malaria; Immune response; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-022-04237-z; https://doaj.org/article/97a0125e16da41cb923ae05e31835e96

Abstract Background Interleukin (IL)-4 had been linked to malaria severity, but the findings are controversial, and the evidence is inconsistent and imprecise. In the current investigation, data on IL-4 levels in patients with severe and uncomplicated malaria were compiled. Methods The systematic review was registered at PROSPERO (CRD42022323387). Searches for relevant articles on IL-4 levels in patients with severe malaria and studies that examined IL-4 levels in both uncomplicated malaria and healthy controls were performed in PubMed, Embase, and Scopus using the search strategy without limitation to publication years or language. The quality of all included studies was evaluated using The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: standards for reporting observational studies. Qualitative and quantitative data syntheses were performed. The random-effects model, which weights each study according to its between- and within-study variance, was used to pool the mean difference (MD) of individual studies. The degree of heterogeneity was determined using Cochran's Q and I2 statistics. Additionally, meta-regression and subgroup analyses were perfomed to investigate possible sources of heterogeneity. The outliers were identified using the leave-one-out method and assessed publication bias using funnel plots, Egger’s test, and a contour-enhanced funnel plot. Results A total of 2300 studies were identified through database searches, and 36 were included for analyses. The meta-analysis results showed lower mean IL-4 levels in severe malaria (434 cases) than in uncomplicated malaria (611 cases) (P = 0.01, pooled MD: −3.36 pg/mL, 95% confidence intervals CI −5.55 to −1.16 pg/mL, I 2 : 98.15%, 11 studies). The meta-analysis results showed no difference in mean IL-4 levels between cerebral malaria (96 cases) and noncerebral severe malaria (108 cases) (P = 0.71, pooled MD: 0.86 pg/mL, 95% CI −3.60 to 5.32 pg/mL, I 2 92.13%, four studies). Finally, no difference was found in mean ...