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.
1
-
In healthy individuals, GM-CSF is barely detectable in the blood
1
-
GM-CSF is produced at sites of tissue inflammation and exerts a local inflammatory response
2
-
Unlike other colony-stimulating factors, GM-CSF is minimally involved in steady-state myelopoiesis
1
By serving as a signaling conduit between tissue-invading lymphocytes and myeloid cells, GM-CSF drives inflammation in both innate and adaptive immune responses.
1
In preclinical models, GM-CSF has been shown to be essential for the initiation of the inflammatory cascade leading to CRS
3
Overproduction of GM-CSF drives excessive inflammation, tissue damage, and enhances the production of other pathogenic cytokines
1
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:
1,4-6
Acute lung injury
Coagulopathy
Vascular damage
Multiple organ damage
C-reactive protein (CRP) levels at hospital admission can be used to inform clinical decision making
7
For US Healthcare Professionals Only
References:
1.
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.
2.
Becher B, Tugues S, Greter M. GM-CSF: from growth factor to central mediator of tissue inflammation. Immunity. 2016;45(5):963-973.
3.
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.
4.
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.
5.
Lee C, Choi WJ. Overview of COVID-19 inflammatory pathogenesis from the therapeutic perspective. Arch Pharm Res. 2021;44(1):99-116.
6.
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.
7.
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.