Abstract
Dengue fever is an infection by the dengue virus (DENV) transmitted by vector mosquitoes. It causes many infections in tropical and subtropical countries every year, thus posing a severe disease threat. Cytokine storms, one condition where many proinflammatory cytokines are mass-produced, might lead to cellular dysfunction in tissue/organ failures and often facilitate severe dengue disease in patients. Interleukin- (IL-) 18, similar to IL-1β, is a proinflammatory cytokine produced during inflammation following inflammasome activation. Inflammatory stimuli, including microbial infections, damage signals, and cytokines, all induce the production of IL-18. High serum IL-18 is remarkably correlated with severely ill dengue patients; however, its possible roles have been less explored. Based on the clinical and basic findings, this review discusses the potential immunopathogenic role of IL-18 when it participates in DENV infection and dengue disease progression based on existing findings and related past studies.
Highlights
Dengue disease is a primary Flaviviridae infection worldwide caused by the dengue virus (DENV) [1, 2]
Other evidence from the severe case febrile phase of dengue patients presented a decline in total CD4+ T, T helper (Th) 1, and Th17 cells in contrast to the convalescent phase [40], demonstrating why some patients move to recovery after the critical phase and others developed dysregulated cytokine production that led to fatal DENV infection followed by cytokine release syndrome (CRS) progression
The exciting part is that IL-18 induces Th1 cytokine production but is capable of activating the humoral immune response via Th2 cytokine production. This phenomenon was first examined in mast cells and basophils cultured with IL-3, a factor required for hematopoietic proliferation and survival, exhibiting high IL-18Rα expression
Summary
Dengue disease is a primary Flaviviridae infection worldwide caused by the dengue virus (DENV) [1, 2]. DENV comprises four different serotypes (DENV1 to 4), with a wide range of genotypes and variants [3]. This myriad of DENV serotypes and variants are hypothesized to mediate its survival, together with increasing infectivity [4]. Symptoms of the dengue diseases are widely varied. It could be shown as mild flu-like symptoms, mild dengue fever (MDF), to severe symptoms, the severe dengue diseases (SDDs,) in those who are infected. Severe dengue can result in a variety of consequences, including excessive bleeding, organ damage, plasma leakage, and even death [1, 7,8,9]
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