Use of il-6 inhibitors for the treatment of acute chest syndrome in patients suffering from sickle cell disease

Acute chest syndrome (ACS) is a common and potentially lethal form of acute lung injury in sickle cell disease (SCD). Because pathophysiology remains unclear, therapeutic options are limited to supportive care with empiric antibiotics and red cell transfusion in case of aggravation. A role of inflammation mediated by endothelial and immune cells has been suspected but the levels of pro-inflammatory cytokines and chemokines in the lungs during ACS have not yet been investigated. Here the inventors report dramatically high levels of IL6, unlike IL-1β and TNF-α, in the sputum from SCD children during ACS (n=12) compared with non-ACS sputum (n=6). By contrast, plasma IL-6 levels were not significantly increased during ACS (n=12), compared with vaso-occlusive crisis (n=12), steady state (n=12) and 15 healthy controls (n=9). IL-6 levels were more than 0-fold higher in sputum than in plasma, suggesting increased local production by inflammatory cells during ACS. Sputum levels of IL8, CCL2 and CCL3 chemokines were also increased during ACS, which may contribute to the recruitment of innate immune cells, such as neutrophils and monocytes, in the lungs. The results strongly suggest an involvement of these inflammatory mediators in ACS pathophysiology and open new therapeutic perspectives, in particular with IL-6 inhibitors.

Keywords: Repurposing, Sickle Cell Disease, Acute Chest Syndrome, IL-6
Am J Hematol . 2021 Dec 7. doi: 10.1002/ajh.26433. Online ahead of print.



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Aymeric Empereur
Aymeric Empereur
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Rare disease: Yes

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