Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19
(2021) In Journal of Leukocyte Biology 109(1). p.115-120- Abstract
The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells... (More)
The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells were analyzed for cytokines and surface markers by flow cytometry. High levels of IL-6 and measurable levels of IL-8 and TNF, but not IL-1β, were observed in COVID-19 patients. Monocytes from COVID-19 patients had spontaneous production of IL-1β and IL-8 (P = 0.0043), but not of TNF and IL-6, compared to controls. No spontaneous cytokine production was seen in lymphocytes from either patients or controls. Activation with LPS resulted in massive cytokine production by monocytes from COVID-19 patients and healthy controls, but not from sepsis patients. Finally, monocytes from COVID-19 patients produced more IL-1β than from healthy controls (P = 0.0087) when activated. In conclusion, monocytes contribute partly to the ongoing hyperinflammation by production of IL-1β and IL-8. Additionally, they are responsive to further activation. This data supports the notion of IL-1β blockade in treatment of COVID-19. However, the source of the high levels of IL-6 remains to be determined.
(Less)
- author
- Kahn, Robin LU ; Schmidt, Tobias LU ; Golestani, Karan LU ; Mossberg, Anki LU ; Gullstrand, Birgitta LU ; Bengtsson, Anders A. LU and Kahn, Fredrik LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cytokine storm, monocytes, COVID-19
- in
- Journal of Leukocyte Biology
- volume
- 109
- issue
- 1
- pages
- 6 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:32794348
- scopus:85089388847
- ISSN
- 0741-5400
- DOI
- 10.1002/JLB.5COVBCR0720-310RR
- language
- English
- LU publication?
- yes
- id
- afda4fff-b217-4185-b833-1cfe30e24475
- date added to LUP
- 2021-01-07 12:16:53
- date last changed
- 2024-06-13 03:35:41
@article{afda4fff-b217-4185-b833-1cfe30e24475,
abstract = {{<p>The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COVID-19 (n = 6) and sepsis (n = 3) were included at Skåne University Hospital, Sweden. Healthy controls were also recruited (n = 5). Cytokines were measured in COVID-19 and sepsis patients using an Immulite immunoassay system. PBMCs were cultured with brefeldin A to allow cytokine accumulation. In parallel, LPS was used as an activator. Cells were analyzed for cytokines and surface markers by flow cytometry. High levels of IL-6 and measurable levels of IL-8 and TNF, but not IL-1β, were observed in COVID-19 patients. Monocytes from COVID-19 patients had spontaneous production of IL-1β and IL-8 (P = 0.0043), but not of TNF and IL-6, compared to controls. No spontaneous cytokine production was seen in lymphocytes from either patients or controls. Activation with LPS resulted in massive cytokine production by monocytes from COVID-19 patients and healthy controls, but not from sepsis patients. Finally, monocytes from COVID-19 patients produced more IL-1β than from healthy controls (P = 0.0087) when activated. In conclusion, monocytes contribute partly to the ongoing hyperinflammation by production of IL-1β and IL-8. Additionally, they are responsive to further activation. This data supports the notion of IL-1β blockade in treatment of COVID-19. However, the source of the high levels of IL-6 remains to be determined.</p>}},
author = {{Kahn, Robin and Schmidt, Tobias and Golestani, Karan and Mossberg, Anki and Gullstrand, Birgitta and Bengtsson, Anders A. and Kahn, Fredrik}},
issn = {{0741-5400}},
keywords = {{cytokine storm, monocytes; COVID-19}},
language = {{eng}},
number = {{1}},
pages = {{115--120}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Leukocyte Biology}},
title = {{Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19}},
url = {{http://dx.doi.org/10.1002/JLB.5COVBCR0720-310RR}},
doi = {{10.1002/JLB.5COVBCR0720-310RR}},
volume = {{109}},
year = {{2021}},
}