Are we fully exploiting type I Interferons in today's fight against COVID-19 pandemic?

Aricò, Eleonora; Bracci, Laura; Castiello, Luciano; Gessani, Sandra; Belardelli, Filippo

doi:10.1016/j.cytogfr.2020.07.010

Cited by 18 publications

(26 citation statements)

References 62 publications

(75 reference statements)

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“…While today IFN-I have been largely replaced by new drugs in the clinical practice in patients with cancer and viral or autoimmune diseases, the most recent knowledge on the complex roles of these cytokines under different pathologic conditions reveals new and more selective strategies for their clinical use [ 23 , 116 ]. Novel and potentially more effective modalities of using these cytokines should take into account the IFN effects on cell metabolism at different tissue levels and under various physiological conditions, including hyperglycemia and obesity.…”

Section: Perspectives and Future Directionsmentioning

confidence: 99%

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

Gessani

Belardelli

2021

Cancers

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Type I interferons (IFN-I) are antiviral cytokines endowed with multiple biological actions, including antitumor activity. Studies in mouse models and cancer patients support the concept that endogenous IFN-I play important roles in the control of tumor development and growth as well as in response to several chemotherapy/radiotherapy treatments. While IFN-I signatures in the tumor microenvironment are often considered as biomarkers for a good prognostic response to antitumor therapies, prolonged IFN-I signaling can lead to immune dysfunction, thereby promoting pathogen or tumor persistence, thus revealing the “Janus face” of these cytokines in cancer control, likely depending on timing, tissue microenvironment and cumulative levels of IFN-I signals. Likewise, IFN-I exhibit different and even opposite effects on obesity, a pathologic condition linked to cancer development and growth. As an example, evidence obtained in mouse models shows that localized expression of IFN-I in the adipose tissue results in inhibition of diet–induced obesity, while hyper-production of these cytokines by specialized cells such as plasmacytoid dendritic cells in the same tissue, can induce systemic inflammatory responses leading to obesity. Further studies in mouse models and humans should reveal the mechanisms by which IFN-I can regulate both tumor growth and obesity and to understand the role of factors such as genetic background, diet and microbioma in shaping the production and action of these cytokines under physiological and pathological conditions.

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Section: Perspectives and Future Directionsmentioning

confidence: 99%

Type I Interferons as Joint Regulators of Tumor Growth and Obesity

Gessani

Belardelli

2021

Cancers

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“…Although the use of the pulmonary route represents an asset in terms of therapeutic precision, lack of knowledge of IFN nebulization remains a major limitation (Aricò et al, 2020). In order to apply this therapeutic modality to COVID-19, we explored the possibility of nebulizing IFN-β-1b.…”

Section: Discussionmentioning

confidence: 99%

“…This limit was also highlighted by Jalkanen et al, who suggested to use the parenteral route in order to achieve more efficacious concentrations (Jalkanen et al, 2020). Higher, more specifically pulmonary concentrations could be obtained with inhaled IFN, but available pharmaceutical forms and pharmacokinetic data on this method of administration remain limited in the Western world (Aricò et al, 2020).…”

Section: Toward the Use Of Type I Interferon Via Inhalationmentioning

confidence: 99%

Rationale for COVID-19 Treatment by Nebulized Interferon-β-1b–Literature Review and Personal Preliminary Experience

et al. 2020

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The inflammatory response to COVID-19 is specifically associated with an impaired type I interferon (IFN) response and complete blockade of IFN-β secretion. Clinically, nebulization of IFN-α-2b has been historically used in China to treat viral pneumonia associated with SARS-CoV. Very recent data show that the use of inhaled type I IFN is associated with decreased mortality in Chinese COVID-19 patients. However, IFN nebulization is currently not standard in Europe and the United States. Therefore, our group has set up a project aimed to evaluate the possibility to nebulize IFN-β-1b (a drug currently used in Europe to treat multiple sclerosis via subcutaneous injections) and to assess the safety of this new mode of administration in SARS-CoV-2 infected patients. We present here literature data that allowed us to build our hypothesis and to develop collaboration between clinical pharmacists, intensivists and nebulization engineers in order to gain first pre-clinical and clinical experience of IFN-β-1b nebulization. After validation of the nebulization method and verification of droplet size compatible with nebulization, the method has been applied to four intensive care patients treated at our university hospital, for whom none of the COVID-19 therapies initially used in France led to significant clinical improvement. All patients exhibited negative viral carriage and experienced clinical improvement 7–16 days after having initiated nebulized IFN-β-1b inhalation therapy. No side effects were observed. All patients were alive within a 90-days follow-up. Although it is not possible to draw firm conclusions on treatment efficacy based on this case report, our study shows that pulmonary IFN-β-1b administration is feasible, with a good safety profile. This procedure, which presents the advantage of directly targeting the lungs and reducing the risks of systemic side effects, may represent a promising therapeutic strategy for the care of patients with severe COVID-19. However, our preliminary observation requires confirmation by randomized controlled trials.

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“…The associated diseased condition was termed COVID-19 by the World Health Organization (WHO) [ 1 ]. The WHO announced SARS-CoV-2 virus infection a pandemic as it infected nearly 9 million persons, and engulfed more than 460,000 worldwide [ 2 ]. SARS-CoV-2 is a member of β coronaviruses, consisting of ∼30 kb single-stranded positive-sense RNA as genetic material [ 3 ].…”

Section: Introductionmentioning

confidence: 99%