Normal Free Interleukin-18 (IL-18) Plasma Levels in Dengue Virus Infection and the Need To Measure Both Total IL-18 and IL-18 Binding Protein Levels

Michels, Meta; Mast, Quirijn de; Netea, Mihai G.; Joosten, Leo A. B.; Dinarello, Charles A.; Rudiman, Pandji Irani Fianza; Sinarta, Sylvia; Wisaksana, Rudi; Alisjahbana, Bachti; Ven, A.J.A.M. van der

doi:10.1128/cvi.00147-15

Cited by 33 publications

(28 citation statements)

References 18 publications

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“…Interestingly, although IL-18BPa was elevated in our current cohort, the proportion of IL-18BPa to IL-18 was similar among controls and diabetics. This is consistent with other reports which demonstrate IL-18BP and IL-18 increasing and decreasing concordantly (54,55), except in unique pathologies (56). While a provocative finding, the elevation of IL-18BPa raises the questions of source and cause.…”

Section: Cytokinessupporting

confidence: 92%

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

et al. 2020

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Multiple environmental triggers have been proposed to explain the increased incidence of type 1 diabetes (T1D). These include viral infections, microbiome disturbances, metabolic disorders, and vitamin D deficiency. Here, we used ELISA to examine blood plasma from juvenile T1D subjects and age-matched controls for the abundance of several circulating factors relevant to these hypotheses. We screened plasma for sCD14, mannose binding lectin (MBL), lipopolysaccharide binding protein (LBP), c-reactive protein (CRP), fatty acid binding protein 2 (FABP2), human growth hormone, leptin, total adiponectin, high molecular weight (HMW) adiponectin, total IgG, total IgA, total IgM, endotoxin core antibodies (EndoCAbs), 25(OH) vitamin D, vitamin D binding protein, IL-7, IL-10, IFN-γ, TNF-α, IL-17A, IL-18, and IL-18BPa. Subjects also were tested for prevalence of antibodies targeting adenovirus, parainfluenza 1/2/3, Coxsackievirus, cytomegalovirus, Epstein-Barr virus viral capsid antigen (EBV VCA), herpes simplex virus 1, and Saccharomyces cerevisiae. Finally, all subjects were screened for presence and abundance of autoantibodies targeting islet cell cytoplasmic proteins (ICA), glutamate decarboxylase 2 (GAD65), zinc transporter 8 (ZNT8), insulinoma antigen 2 (IA-2), tissue transglutaminase, and thyroid peroxidase, while β cell function was gauged by measuring c-peptide levels. We observed few differences between control and T1D subjects. Of these, we found elevated sCD14, IL-18BPa, and FABP2, and reduced total IgM. Female T1D subjects were notably elevated in CRP levels compared to control, while males were similar. T1D subjects also had significantly lower prevalence of EBV VCA antibodies compared to control. Lastly, we observed that c-peptide levels were significantly correlated with leptin levels among controls, but this relationship was not significant among T1D subjects. Alternatively, adiponectin levels were significantly correlated with c-peptide levels among T1D subjects, while controls showed no relationship between these two factors. Among T1D subjects, the highest c-peptide levels were associated with the lowest adiponectin levels, an indication of insulin resistance. In total, from our examination we found limited data that strongly support Harms et al. Confirmation and Identification of Biomarkers any of the hypotheses investigated. Rather, we observed an indication of unexplained monocyte/macrophage activation in T1D subjects judging from elevated levels of sCD14 and IL-18BPa. These observations were partnered with unique associations between adipokines and c-peptide levels among T1D subjects.

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Section: Cytokinessupporting

confidence: 92%

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

et al. 2020

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“…We found that although serum IL-18 levels were higher in patients with DHF compared to those with DF, especially during early illness, these differences were not significant at any time point ( Figure 3A). The median values of IL-18 seen throughout the course of illness was similar to the values observed previously in patients with DHF (median values 409.5 pg/ml in early illness to 352.3 pg/ml in late illness) and DF (median values 327.1 pg/ml in early illness to 224.2 pg/ml in late illness) ( Fig 3A)[28] and were several folds higher than IL-18 levels seen in healthy individuals [28]. However, serum IL-18 levels did show a statistically significant but weak correlation with serum LPS levels (Spearman's r=0.20, p=0.009) ( Figure 3B).…”

Section: Association Of Serum Il-18 and Lps In Patients With Acute Desupporting

confidence: 88%

The association of lipopolysaccharide and inflammatory markers with severe dengue infection

Shyamali¹,

Mahaputuna²,

Gomes³

et al. 2019

Preprint

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Background Although serum lipopolysaccharide (LPS) was shown to associate with development of severe dengue, the reasons for high LPS and its subsequent involvement in disease pathogenesis are not known. Methods: We assessed LPS, lipopolysaccharide binding protein (LBP), CRP, IL-18, procalcitonin in patients with acute dengue fever (DF=129) and dengue haemorrhagic fever (DHF=64) and correlated these observations with the presence of comorbid illnesses, concurrent bacteraemia and clinical disease severity. Results: LPS levels were significantly (p=0.01) higher in patients with DHF, compared to those with DF. 45 (70%) of those with DHF and 63 (49%) of those with DF had detectable LPS and therefore, presence of LPS was significantly associated with DHF (p=0.005, OR=2.48, 95% CI: 1.29 to 4.64). Those with metabolic diseases, 22/29 (75.9%) and those with atopic diseases 17/22 (77.3%) were significantly more likely to have detectable LPS (p=0.025, OR=2.9, 95% CI- 1.17 to 7.59) and (p=0.039, OR=3.06, 95% CI-1.07 to 7.81) respectively, than others. LPS, LBP and CRP levels were high at the febrile phase, before onset of plasma leakage and reduced towards to the critical phase. The CRP levels were significantly higher (p=0.03) in early illness (≤3 days of illness) in those who progressed to develop DHF when compared to those who developed DF. Those who had detectable serum LPS also had a significantly higher CRP (p=0.01). Although there was no difference in procalcitonin (PCT) levels in patients with DF and DHF, the PCT levels were significantly higher in those who had detectable serum LPS (p=0.02). Conclusions: LPS levels were higher in patients with DHF and associated with high levels of other inflammatory markers. Since LPS levels were highest during early infection and were significantly more likely to be present in those with comorbid illnesses, the possible role of LPS in disease pathogenesis, should be further investigated.

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“…For IG measurements – reported as percentage of total leukocyte count or as absolute numbers – the membranes of mature WBC were first partly lysed before analyzing light scatter properties and the nucleic acid content of the cells in the leukocyte differentiation channel. The laboratory confirmation of dengue, leptospirosis, and enteric fever diagnosis was made as previously described for this cohort .…”

Section: Methodsmentioning

confidence: 99%

New parameters available on Sysmex XE‐5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever

Oehadian

Michels

Mast

et al. 2015

Int J Lab Hematology

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Normal Free Interleukin-18 (IL-18) Plasma Levels in Dengue Virus Infection and the Need To Measure Both Total IL-18 and IL-18 Binding Protein Levels

Cited by 33 publications

References 18 publications

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

The association of lipopolysaccharide and inflammatory markers with severe dengue infection

New parameters available on Sysmex XE‐5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever

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