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CYCLOSPORIN H: A NOVEL ANTI-INFLAMMATORY THERAPY FOR INFLUENZA FLU PATIENTS

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Last updated: 04 Jan 2025

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Abstract

Relatively little is known about the inflammatory mediators and mechanisms that drive the progression of influenza flu infection to cytokine storm, lung dysfunction, organ failure, and ultimately death. Vaccines and antiviral medications cannot control the excessive host inflammatory response associated with severe influenza flu infection. Studies by Elgebaly et al demonstrated the rapid release of a potent inflammatory mediator, recently named Nourin, by local mammalian tissues in response to injury and infection. Nourin is a formyl peptide that acts through the formyl peptide receptor (FPR) on phagocytic leukocytes. As an initial signal in the innate immunity, Nourin stimulates leukocyte chemotaxis, induces acute and chronic inflammation, and stimulates the release of a number of the cytokine storm mediators from monocytes, neutrophils and endothelial cells. Furthermore, Nourin detected in plasma samples from patients with severe influenza infection was much higher compared to moderate influenza. The Nourin antagonist, Cyclosporin H, is a potent anti-inflammatory compound, which acts as a specific competitive antagonist of formyl peptides on the formyl peptide receptor (FPR) on phagocytic leukocytes. Cyclosporin H completely blocked neutrophil chemotaxis induced by: (a) the standard formyl peptide, f-MLF, (b) the Staphylococcus aureus bacteria-derived formyl peptide
Phenol-soluble modulins, such as PSM3a, plus(c) the host-derived Nourin released by: (1) cultured epithelial cells infected with the PR8 H1N1 influenza virus for 6 to 24 hours, (2) Nourin detected in the serum of mouse model of H1N1 Swine flu influenza infection for 6 hours , along with (3) Nourin detected in plasma samples collected from severe and moderate influenza patients. Furthermore, in-vivo treatment by Cyclosporin H in the mouse model of H1N1 Swine flu influenza infection for 5 days markedly reduced lung inflammation and endothelial cell damage. Thus, two clinical applications for Nourin and its antagonist Cyclosporin H are proposed: Diagnostic Application: The blood Nourin test can be used as a key inflammatory biomarker for “early" detection and monitoring of influenza flu patients proceeding to hyperactive inflammation and, thus, permitting early crucial anti-inflammatory therapy. Therapeutic Application: Cyclosporin H will specifically block Nourin as an important initial stimulant of cytokine mediators, and thus can control the development and progression of cytokine storm plus organ inflammation, which usually initiates 3 to 8 days post influenza. Since Cyclosporin H does not target the virus, it will not develop drug resistance and will reduce the host uncontrolled inflammatory response, induced by both new strains of flu viruses and existing viruses with mutations.

DOI

10.21608/jesp.2017.77960

Keywords

Influenza Flu virus, Cytokine Storm, Formyl Peptide Nourin, Formyl Peptide Receptor, Formyl Peptide Competitive Antagonist, Cyclosporin H, Anti-Inflammatory Therapy, Diagnostic Inflammatory Biomarker, Methicillin-resistant Staph. aureus (MRSA)

Authors

First Name

SALWA

Last Name

ELGEBALY

MiddleName

A.

Affiliation

Nour Heart, Inc., Biotech Company, Germantown, Maryland, United States of America.

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First Name

TAMER

Last Name

ELBAYOUMI

MiddleName

-

Affiliation

College of Pharmacy-Glendale/Nanomedicine Center of Excellence in Translational Cancer Research.

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First Name

DONALD

Last Name

KREUTZER

MiddleName

L.

Affiliation

Midwestern University, Arizona, United States of America; University of Connecticut Faculty of Medicine, Farmington, Connicticut, United States of America.

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Volume

47

Article Issue

1

Related Issue

11647

Issue Date

2017-04-01

Receive Date

2020-03-18

Publish Date

2017-04-01

Page Start

25

Page End

33

Print ISSN

1110-0583

Online ISSN

2090-2549

Link

https://jesp.journals.ekb.eg/article_77960.html

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https://jesp.journals.ekb.eg/service?article_code=77960

Order

4

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Original Article

Type Code

1,127

Publication Type

Journal

Publication Title

Journal of the Egyptian Society of Parasitology

Publication Link

https://jesp.journals.ekb.eg/

MainTitle

CYCLOSPORIN H: A NOVEL ANTI-INFLAMMATORY THERAPY FOR INFLUENZA FLU PATIENTS

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Article

Created At

22 Jan 2023