Abstract
BACKGROUND: Interleukin (IL)-1β is a proinflammatory cytokine that has a role in disease-related inflammation, including malaria. However, reports on the effect of IL-1β on malaria severity are inconsistent. Therefore, meta-analyses to compare differences in IL-1β levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls were performed. METHODS: The PRISMA standards were used to perform a systematic review and meta-analysis. A search of PubMed, Scopus, EMBASE and reference lists was conducted for articles providing data on IL-1β levels between patients with severe malaria, patients with uncomplicated malaria and healthy controls between January 1988 and March 2022, using a combination of search terms. The quality of all studies included in this review was determined using the Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies. The evidence was synthesized quantitatively and qualitatively. The differences in IL-1 levels across participant groups were recounted narratively for qualitative synthesis. For quantitative synthesis, the mean difference in IL-1β levels across groups of participants was calculated using a random effects meta-analysis. The publication bias was assessed using funnel plots, Egger's test and a contour-enhanced funnel plot. RESULTS: A total of 1281 articles were discovered, and the 17 that satisfied the inclusion criteria were included for syntheses. The meta-analysis results using data from 555 cases of severe malaria and 1059 cases of uncomplicated malaria showed that severe malaria had a higher mean of IL-1β levels than uncomplicated malaria (P < 0.01, pooled mean difference: 1.92 pg/mL, 95% confidence interval: 0.60-3.25 pg/mL, I(2): 90.41%, 6 studies). The meta-analysis results using data from 542 cases of uncomplicated malaria and 455 healthy controls showed no difference in mean IL-1β levels between the two groups (P = 0.07, pooled mean difference: 1.42 pg/mL, 95% confidence interval: - 0.1-2.94 pg/mL, I(2): 98.93%, 6 studies). CONCLUSION: The results from the meta-analysis revealed that IL-1β levels were higher in patients with severe malaria than in patients with uncomplicated malaria; however, IL-1β levels were similar in patients with uncomplicated malaria and healthy controls. Based on the limitations of the number of studies included in the meta-analysis and high levels of heterogeneity, further studies are needed to conclude that differences in IL-1β levels can be useful for monitoring the malaria severity.