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GM-CSF: A MYELOID
INFLAMMATORY FACTOR

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

GM-CSF is a pro-inflammatory cytokine linked to myeloid-driven inflammation, including the hyperinflammation associated with cytokine release syndrome (CRS) or cytokine storm.

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  • In healthy individuals, GM-CSF is barely detectable in the blood

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  • GM-CSF is produced at sites of tissue inflammation and exerts a local inflammatory response

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  • Unlike other colony-stimulating factors, GM-CSF is minimally involved in steady-state myelopoiesis

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By serving as a signaling conduit between tissue-invading lymphocytes and myeloid cells, GM-CSF drives inflammation in both innate and adaptive immune responses.

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In preclinical models, GM-CSF has been shown to be essential for the initiation of the inflammatory cascade leading to CRS

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GM-CSF molecule

Overproduction of GM-CSF drives excessive inflammation, tissue damage, and enhances the production of other pathogenic cytokines

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About Cytokine Storm

Cytokine storm is a myeloid-driven hyperinflammatory response that can result from a viral infection such as SARS-CoV-2 and can have many consequences including:

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Lungs

Acute lung injury

Blood droplets

Coagulopathy

Veins branching

Vascular damage

Kidney and bladder

Multiple organ damage

C-reactive protein (CRP) levels at hospital admission can be used to inform clinical decision making

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For US Healthcare Professionals Only

References:

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Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020;20(8):507-514.

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Becher B, Tugues S, Greter M. GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity. 2016;45(5):963-973.

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Sentman ML, Murad JM, Cook WJ, et al. Mechanisms of acute toxicity in NKG2D chimeric antigen receptor T cell-treated mice. J Immunol. 2016;197(12):4674-4685.

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Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, et al. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6(57):eabg9873. 

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Lee C, Choi WJ. Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective. Arch Pharm Res. 2021;44(1):99-116.

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Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793.

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Manson JJ, Crooks C, Naja M, et al. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. Lancet Rheumatol. 2020;2(10):e594-e602.