Increased serum ferritin and interleukin-18 levels in children with dengue

Abstract

Activated monocytes/macrophages that produce a cytokine storm play an important role in the pathogenesis of dengue. Interleukin-18 (IL-18) is a proinflammatory cytokine produced by monocyte/macrophages that is increased during dengue. Ferritin is an acute-phase reactant and expressed by cells of the reticulo-endothelial system in response to infection by dengue virus. The aims of this study were to analyze the simultaneous expression of both IL-18 and ferritins in children infected by diverse serotypes of dengue virus (DENV) and determine their association with dengue severity. In this regard, children with dengue (n = 25) and healthy controls with similar age and sex (n = 20) were analyzed for circulating ferritin and cytokines. Monocytes were isolated by Hystopaque gradient and co-cultured with DENV-2. IL-18 and ferritin contents in blood, and IL-18 in culture supernatants were determined by ELISA. Increased levels of ferritin and IL-18 (p < 0.0001) were observed in dengue patients, not associated to NS1expression or type of infection (primary or secondary). Highest values of both molecules (p < 0.001) were observed in dengue with warning signs and severe dengue. Differential effect on IL-18/ferritin production was observed associated to viral serotype infection. There were no correlations between ferritin vs. IL-18 production, ferritin vs. NS1 status, and IL-18 vs. NS1 status. Viral-infected monocyte cultures showed increased production of IL-18 (p < 0.001). In conclusion, increased circulating ferritin and IL-18 are expressed in children infected by different serotypes of DENV associated with dengue severity.

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19

“…Nevertheless, IL-18 is suggested to be beneficial in early host defense in viral infections since the IL-18 knock down animal has reduced survival with murine coronavirus infection [27] . However, aberrant or long standing IL-18 activation can also lead to severe pathological injury as shown in avian influenza and Dengue virus infections [18] , [19] .…”

“…The activity of IL-18 is balanced by IL-18 binding protein (IL-18BP) which is stimulated by IFN-γ, prompting a classical feedback loop whereby IL-18BP offsets exuberant IL-18 and attenuates the IFN-γ response [17] . Markedly elevated serum IL-18 levels have been linked to severe disease and mortality in some viral infections characterized by cytokine storm such as avian influenza and Dengue virus [18] , [19] .…”

Atypical Manifestations of Dengue Fever in Children

“…15 The incidence of dengue-associated HLH in previous studies is 2.3%. 5,6 However, hyperferritinemia is common in dengue and can be a useful predictor of severe dengue. 16 Serum ferritin value > 3000 ng/mL is associated with higher mortality.…”

“…Those with five out of eight HLH 2014 diagnostic criteria were described as proven HLH and those with 3 to 4 criteria were described as hyperferritinemia-associated immune dysregulation. [4][5][6] The inclusion criteria for "atypical manifestation" were as follows:…”

A Mendelian Randomization Analysis to Expose the Causal Effect of IL-18 on Osteoporosis Based on Genome-Wide Association Study Data

“…IL-18 is one of them, which locates at 11q22.2-22.3. IL-18 is powerful inflammatory cytokines, the most characteristic feature of which is the regulation of cellular proliferation and differentiation (Weiss et al, 2018;Youssef et al, 2018;Prencipe et al, 2019;Valero et al, 2019). Recent studies show that IL-18 plays important roles in immune regulation, resistance to infection and anti-tumor.…”