Serum levels of interleukin-6 are linked to the severity of the disease caused by Andes Virus

Abstract

Andes virus (ANDV) is the etiological agent of hantavirus cardiopulmonary syndrome in Chile. In this study, we evaluated the profile of the pro-inflammatory cytokines IL-1β, IL-12p70, IL-21, TNF-α, IFN-γ, IL-10 and IL-6 in serum samples of ANDV-infected patients at the time of hospitalization. The mean levels of circulating cytokines were determined by a Bead-Based Multiplex assay coupled with Luminex detection technology, in order to compare 43 serum samples of healthy controls and 43 samples of ANDV-infected patients that had been categorized according to the severity of disease. When compared to the controls, no significant differences in IL-1β concentration were observed in ANDV-infected patients (p = 0.9672), whereas levels of IL-12p70 and IL-21 were significantly lower in infected cases (p = <0.0001). Significantly elevated levels of TNF-α, IFN-γ, IL-10, and IL-6 were detected in ANDV-infected individuals (p = <0.0001, 0.0036, <0.0001, <0.0001, respectively). Notably, IL-6 levels were significantly higher (40-fold) in the 22 patients with severe symptoms compared to the 21 individuals with mild symptoms (p = <0.0001). Using multivariate regression models, we show that IL-6 levels has a crude OR of 14.4 (CI: 3.3–63.1). In conclusion, the serum level of IL-6 is a significant predictor of the severity of the clinical outcome of ANDV-induced disease.

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus‐associated syndromes

“…This has led to the introduction of successful anti‐IL‐6R treatment of severe CRS . In relation to recent findings from our own laboratory , and other laboratories , increased levels of IL‐6 have also been observed and found to be associated with severe disease in hantavirus infection caused by Andes and Puumala viruses. This finding suggests the possibility of trying similar anti‐IL‐6R therapeutic strategies for treatment in the most severe cases of hantavirus infection.…”

“…Elevated IL‐6 levels in plasma have been associated with more severe HFRS . Elevated levels of IL‐6 and other cytokines such as IL‐8, IL‐10, TNF and IFN‐γ have also been detected in Dobrava virus‐infected and Hantaan virus‐infected HFRS patients and in HPS patients indicating that elevated levels of these cytokines are a general consequence of human hantavirus infection.…”

RIG-I-like receptor activation drives type I IFN and antiviral signaling to limit Hantaan orthohantavirus replication

“…Although, the vascular endothelium is the primary cellular target of hantavirus infection in both humans and in reservoir hosts, infection drives very different outcomes of acute pathogenesis in humans while persistent, nonpathogenic infection occurs in reservoir hosts [10]. Hantavirus disease in humans begins with intense muscle pain, fever, and nausea, accompanied by elevated levels of the proinflammatory cytokines IL-1β, TNFα, and IL-6 and others [2,[11][12][13]. Vascular leakage, either in the lung microvasculature or kidneys, is the hallmark of disease and can be linked to lethal disease.…”

Characterization of Oral Immunity in Cases and Close Household Contacts Exposed to Andes Orthohantavirus (ANDV)

“…ANDV-induced illness is associated with the activation of the host's innate immune response. An elevated concentration of circulating TNFα, IFNγ, IL10, and IL6 were observed in ANDV-infected patients compared to healthy subjects (Angulo et al, 2017). Moreover, IL6 levels were associated with more severe symptoms (Angulo et al, 2017;Maleki et al, 2019).…”

“…In order to evaluate if our findings were related to a local or to a systemic inflammatory response, we compared cytokines concentration in saliva and serum samples obtained concomitantly in 33 ANDV-infected patients during the acute stage of disease. For each individual, a fold increase of each cytokine concentration was calculated compared to median concentration of healthy subjects in saliva and serum samples [median concentration in saliva samples from 38 healthy controls not exposed; median concentration in serum of healthy subjects as described in literature (Kleiner et al, 2013;Angulo et al, 2017;Maleki et al, 2019)]. Results were organized in a heatmap analysis (Figure 3).…”