Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection

Percopo, Caroline M.; Ma, Michelle; Brenner, Todd A.; Krumholz, Julia O.; Break, Timothy J.; Laky, Karen; Rosenberg, Helene F.

doi:10.4049/jimmunol.1800927

Cited by 38 publications

(47 citation statements)

References 84 publications

(112 reference statements)

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“…Part of the explanation is that there are no mild cases in this study (see section “Materials and Methods”). More importantly, although the role of IL-6 in the pathological development of COVID-19 has attracted much attention ( 3 ), its specific role remains controversial ( 9 – 12 ), and several experimental models of viral lung infections suggest that IL-6 demonstrates either pathogenic ( 39 )or protective ( 40 ) effects in vivo ; the consequences of IL-6 induction in COVID-19 may vary depending on the stage of infection and the immune status of the host. The role of these cytokines in SARS-CoV-2 infection should be carefully evaluated.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19

et al. 2020

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 ( P < 0.001, P = 0.024) and to CD3 + and CD8 + T lymphocytes ( P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease ( P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge ( P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease ( P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.

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Section: Discussionmentioning

confidence: 99%

Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19

et al. 2020

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“…Moreover, the expression of pro-inflammatory mediators in the lungs due to RSV infection decreased, while interferon-stimulated genes were upregulated by L. gasseri treatment [ 77 ]. A reduction of virus-induced inflammation was also exerted by a strain of L. plantarum in mice after acute infection by pneumonia virus (PMV), a rodent pathogen that induces inflammation and is related to the respiratory syncytial virus [ 78 ]. Bifidobacterium animalis subspecies lactis Bl-04, in an experimental rhinovirus infection, showed to reduce the levels of the pro-inflammatory cytokine IL-6, as well as to reduce the nasal lavage virus titer [ 79 ].…”

Section: Probioticsmentioning

confidence: 99%

Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review

et al. 2020

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The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.

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“…Inflammation and associated pulmonary edema were evaluated quantitatively as previously described [23,24]. Briefly, whole lungs were removed from Inf A-infected and A. alternata-challenged and Inf A-infected mice.…”

Section: Lung Wet-to-dry Measurementsmentioning

confidence: 99%

Alternaria alternata Accelerates Loss of Alveolar Macrophages and Promotes Lethal Influenza A Infection

Percopo

Mai

et al. 2020

Viruses

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Chronic inhalation of fungi and fungal components has been linked to the development of respiratory disorders, although their role with respect to the pathogenesis of acute respiratory virus infection remains unclear. Here, we evaluate inflammatory pathology induced by repetitive administration of a filtrate of the ubiquitous fungus, Alternaria alternata, and its impact on susceptibility to infection with influenza A. We showed previously that A. alternata at the nasal mucosae resulted in increased susceptibility to an otherwise sublethal inoculum of influenza A in wild-type mice. Here we demonstrate that A. alternata-induced potentiation of influenza A infection was not dependent on fungal serine protease or ribonuclease activity. Repetitive challenge with A. alternata prior to virus infection resulted proinflammatory cytokines, neutrophil recruitment, and loss of alveolar macrophages to a degree that substantially exceeded that observed in response to influenza A infection alone. Concomitant administration of immunomodulatory Lactobacillus plantarum, a strategy shown previously to limit virus-induced inflammation in the airways, blocked the exaggerated lethal response. These observations promote an improved understanding of severe influenza infection with potential clinical relevance for individuals subjected to continuous exposure to molds and fungi.

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Critical Adverse Impact of IL-6 in Acute Pneumovirus Infection

Cited by 38 publications

References 84 publications

Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19

Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19

Diet Supplementation, Probiotics, and Nutraceuticals in SARS-CoV-2 Infection: A Scoping Review

Alternaria alternata Accelerates Loss of Alveolar Macrophages and Promotes Lethal Influenza A Infection

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