tetano
Editor, Senior Moderator
Viral Immunol
. 2022 Jan 27.
doi: 10.1089/vim.2021.0111. Online ahead of print.
Tocilizumab-Induced Unexpected Increase of Several Inflammatory Cytokines in Critically Ill COVID-19 Patients: The Anti-Inflammatory Side of IL-6
Fanny Ponthieux[SUP] 1 [/SUP], Nicolas Dauby[SUP] 2 3 [/SUP], Evelyne Maillart[SUP] 4 [/SUP], Jean-François Fils[SUP] 5 [/SUP], Julie Smet[SUP] 1 [/SUP], Marc Claus[SUP] 6 [/SUP], Tatiana Besse-Hammer[SUP] 7 [/SUP], David De Bels[SUP] 8 [/SUP], Francis Corazza[SUP] 1 9 [/SUP], Carole Nagant[SUP] 1 [/SUP]
Affiliations
Abstract
Early evidence during the coronavirus disease 2019 (COVID-19) pandemic indicated high levels of interleukin (IL)-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic. While the monoclonal antibody blocks IL-6 pathway, its effect on other inflammatory cytokines remains poorly described. To better understand the effect of TCZ on the biological inflammatory profile, we monitored a large panel of inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Twenty-three patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were included in the study, among which 15 patients received TCZ and 8 patients did not. Serum samples were collected for 8 days, before and following TCZ administration or hospital admission for the control group. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), and sIL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18, and sIL-6R levels in the treated patients with maximal values reaching 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. Our results suggested that some inflammatory pathways escape IL-6R blockade and even appeared amplified. This finding highlights an old observation of the anti-inflammatory effects of IL-6 as already suggested over 20 years ago. Clinical Trial Registration number: NCT04346017.
Keywords: COVID-19; IL-6; SARS-CoV-2 infection; cytokines; inflammation; tocilizumab.
. 2022 Jan 27.
doi: 10.1089/vim.2021.0111. Online ahead of print.
Tocilizumab-Induced Unexpected Increase of Several Inflammatory Cytokines in Critically Ill COVID-19 Patients: The Anti-Inflammatory Side of IL-6
Fanny Ponthieux[SUP] 1 [/SUP], Nicolas Dauby[SUP] 2 3 [/SUP], Evelyne Maillart[SUP] 4 [/SUP], Jean-François Fils[SUP] 5 [/SUP], Julie Smet[SUP] 1 [/SUP], Marc Claus[SUP] 6 [/SUP], Tatiana Besse-Hammer[SUP] 7 [/SUP], David De Bels[SUP] 8 [/SUP], Francis Corazza[SUP] 1 9 [/SUP], Carole Nagant[SUP] 1 [/SUP]
Affiliations
- PMID: 35085462
- DOI: 10.1089/vim.2021.0111
Abstract
Early evidence during the coronavirus disease 2019 (COVID-19) pandemic indicated high levels of interleukin (IL)-6 in patients with severe COVID-19. This led to the off-label use of tocilizumab (TCZ) during the first wave of the pandemic. While the monoclonal antibody blocks IL-6 pathway, its effect on other inflammatory cytokines remains poorly described. To better understand the effect of TCZ on the biological inflammatory profile, we monitored a large panel of inflammatory cytokines in critically ill COVID-19 patients receiving off-label TCZ. Twenty-three patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were included in the study, among which 15 patients received TCZ and 8 patients did not. Serum samples were collected for 8 days, before and following TCZ administration or hospital admission for the control group. Serum profile of 12 cytokines (IL-1β, -2, -4, -6, -8, -10, -12, -13, -17, -18, tumor necrosis factor α (TNF-α), interferon-gamma (IFN-γ), and sIL-6R were assessed in these two groups. Although the increased IL-6 concentrations after TCZ infusion were expected, we observed an unexpected increase in IL-1β, -2, -4, -10, -12p70, -18, and sIL-6R levels in the treated patients with maximal values reaching 2 to 4 days after TCZ. In contrast, no change in cytokine levels was observed in the control group. Our results suggested that some inflammatory pathways escape IL-6R blockade and even appeared amplified. This finding highlights an old observation of the anti-inflammatory effects of IL-6 as already suggested over 20 years ago. Clinical Trial Registration number: NCT04346017.
Keywords: COVID-19; IL-6; SARS-CoV-2 infection; cytokines; inflammation; tocilizumab.