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Table 1 Ex vivo and in vitro immunomodulatory and barrier function effects of LMWF5A

From: The novel immunomodulatory biologic LMWF5A for pharmacological attenuation of the “cytokine storm” in COVID-19 patients: a hypothesis

Cell ModelResultsConclusionsStudy
Influenza HA presented human T-cell cloneLMWF5A and DA-DKP treatment results in:
↓ TNFα
↓ IFNγ
Reduced release of cytokines associated with COVID-19 cytokine storm.[17]
Influenza HA presented and CD3/CD28 stimulated human T-cell cloneDA-DKP treatment results in:
↓ TNFα
↓ IFNγ
↑ RAP-1 phosphorylation and activity
Reduced release of cytokines associated with COVID-19 cytokine storm. Also, increased activation of barrier enhancing GTPase.[18]
LPS-stimulated human PBMCLMWF5A and DA-DKP treatment results in:
↓ TNFα
Reduced release of cytokine associated with COVID-19 cytokine storm.[19]
LPS-stimulated human PBMCLMWF5A treatment results in:
↓ TNFα
↑ PGE2 and 15d-PGJ2
Reduced release of cytokine associated with COVID-19 cytokine storm together with increased pro-resolving mediator release.[20]
LPS-stimulated, PMA-differentiated THP-1 macrophagesLMWF5A treatment results in:
↓ IL-6, IL-12, and CXCL10
↑ IL-10
↑ AhR activity
Reduced release of cytokines associated with COVID-19 cytokine storm with apparent shift from M1 to M2 phenotype.[21]
Monolayer and 3D cultured human BMMSCLMWF5A treatment results in:
↓ RhoA activity
↑ Rac1 activity
↓ Stress fiber formation
↑ Stem cell homing potential
Rebalancing of overall GTPase activity conducive to barrier enhancement. Also, increased progenitor cell homing potential.[22]
Dedifferentiated primary human chondrocytesLMWF5A treatment results in:
↑ SRY-Box transcription factor
↓ Apoptosis
Activation of transcription factor protective of fibrosis and increased cell survival.[23]
Primary human endothelial cell permeability modelsLMWF5A treatment results in:
↑ Acetylation of α-tubulin
↓ Vascular leakage
Enhanced barrier function of endothelial cells with reduced vascular leakage. Also, apparent stabilization of microtubule network.[24]