Interleukin-6, CXCL10 and Infiltrating Macrophages in COVID-19-Related Cytokine Storm: Not One for All But All for One!

Abstract

SARS-COV-2 virus is responsible for the ongoing devastating pandemic. Since the early phase of the pandemic, the “cytokine-storm” appeared a peculiar aspect of SARS-COV-2 infection which, at least in the severe cases, is responsible for respiratory treat damage and subsequent multi-organ failure. The efforts made in the last few months elucidated that the cytokine-storm results from a complex network involving cytokines/chemokines/infiltrating-immune-cells which orchestrate the aberrant immune response in COVID-19. Clinical and experimental studies aimed at depicting a potential “immune signature” of SARS-COV-2, identified three main “actors,” namely the cytokine IL-6, the chemokine CXCL10 and the infiltrating immune cell type macrophages. Although other cytokines, chemokines and infiltrating immune cells are deeply involved and their role should not be neglected, based on currently available data, IL-6, CXCL10, and infiltrating macrophages could be considered prototype factors representing each component of the immune system. It rapidly became clear that a strong and continuous interplay among the three components of the immune response is mandatory in order to produce a severe clinical course of the disease. Indeed, while IL-6, CXCL10 and macrophages alone would not be able to fully drive the onset and maintenance of the cytokine-storm, the establishment of a IL-6/CXCL10/macrophages axis is crucial in driving the sequence of events characterizing this condition. The present review is specifically aimed at overviewing current evidences provided by both in vitro and in vivo studies addressing the issue of the interplay among IL-6, CXCL10 and macrophages in the onset and progression of cytokine storm. SARS-COV-2 infection and the “cytokine storm.”

Sex-Related Differences in Innate and Adaptive Immune Responses to SARS-CoV-2

“…Elevated levels of CXCL-10 have been reported in both the plasma and bronchial alveolar lavage fluid (BALF) and were associated with disease severity in viral infections ( 50 ). Similar findings have been reported for COVID-19 ( 51 – 53 ). CXCL-10 was consistently found to be elevated in the serum of patients with severe COVID-19.…”

“…It acts as a chemoattractant for monocytes/macrophages, DCs, NK cells, and T cells. In the lungs, it is involved in the recruitment of CXCR3-positive macrophages that produce high levels of IL-6 ( 51 ). Elevated levels of CXCL-10 have been reported in both the plasma and bronchial alveolar lavage fluid (BALF) and were associated with disease severity in viral infections ( 50 ).…”

Genome‐scale metabolic modelling of SARS‐CoV‐2 in cancer cells reveals an increased shift to glycolytic energy production

“…4E , MIP‐1β was the most highly expressed cytokine/chemokine at 24 and 48 hpi and was then replaced by IP10 at 72 hpi. IP10 has been reported as a good biomarker of SARS‐CoV‐2 disease progression and severity [ 87 , 88 , 89 ] and has been implicated in the cytokine storm with higher levels leading to more severe disease [ 90 , 91 ]. Eotaxin was the second most highly upregulated protein at 72 hpi followed by AGP and IL‐6, respectively.…”

COVID-19-Associated Subacute Thyroiditis: Evidence-Based Data From a Systematic Review

“…This hypothesis would hold particularly true only for the so-called "second wave" of the pandemic, since corticosteroids were contraindicated by most national guidelines in the early phase of the pandemic (54). It could be thus hypothesized that SAT would be a typical complication of less severe forms of COVID-19 occurring in communitydwelling, young female subjects that are less frequently included in clinical studies, while hospitalized patients would more often experience non-thyroidal illness syndrome due to the hyperinflammatory state typical of severe COVID-19 (55)(56)(57). In this context, a systematic review by Ruggeri et al (58) provided a comprehensive review of all COVID-19-related inflammatory disorders.…”