IL-6 levels are dramatically high in the sputum from children with sickle cell disease during acute chest syndrome

Abstract

Key Points Sputum interleukin-6 (IL-6) level is high during acute chest syndrome (ACS) in pediatric sickle cell disease, supporting anti–IL-6 trials. Sputum IL-8, CCL2, and CCL3 levels are also high during ACS, possibly contributing to recruitment of inflammatory cells in the lungs.

Tocilizumab for severe acute chest syndrome in a child with sickle cell disease and dramatically high interleukin‐6 values in endotracheal and pleural fluids

“…2 We recently reported a major increase in IL-6, unlike other main pro-inflammatory cytokines, in the sputum and bronchoalveolar fluid from SCD children during ACS. 3 These values were more than 150-fold higher than those observed in plasma, suggesting a predominant local inflammation over systemic inflammation. Furthermore, patients with the highest sputum IL-6 values had the most severe forms of ACS, suggesting a positive correlation between IL-6 concentrations and ACS severity.…”

“…2 Selinexor has good oral bioavailability, and is metabolized primarily by multiple hepatic routes without significant renal metabolism. 3 In addition, it does not directly affect creatinine clearance (CrCl), though it can be associated with asymptomatic hyponatremia, which may be due to increased sodium loss from the kidney. 2 Selinexor is approved by the United States Food and Drug Administration for patients with MM after at least one prior therapy based on the BOSTON study, 4 with no contraindications based on renal dysfunction.…”

The Role of Inflammation in the Cellular and Molecular Mechanisms of Cardiopulmonary Complications of Sickle Cell Disease

“…Accumulating evidence has long identified chronic low-grade inflammation as a risk factor for the progression of myocardial infarction, ventricular hypertrophy, cardiac fibrosis, diastolic dysfunction, and pulmonary hypertension in the general population [6][7][8][9][10] . Recent mechanistic and observational studies on cardiopulmonary complications of SCD implicate inflammation as a major player in the onset and progression of cardiopulmonary complications in SCD [11][12][13][14][15][16] . These include several studies in animals and humans on the development of acute chest syndrome (ACS), cardiac hypertrophy, pulmonary hypertension (PH), cardiac fibrosis, and diastolic dysfunction [11][12][13][14][15] .…”

“…Recent mechanistic and observational studies on cardiopulmonary complications of SCD implicate inflammation as a major player in the onset and progression of cardiopulmonary complications in SCD [11][12][13][14][15][16] . These include several studies in animals and humans on the development of acute chest syndrome (ACS), cardiac hypertrophy, pulmonary hypertension (PH), cardiac fibrosis, and diastolic dysfunction [11][12][13][14][15] . These studies consistently suggested inflammatory pathways as a vital unifying mechanism that accompanies the structural and functional changes that occur at the onset and Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s).…”

Sputum IL‐6 level as a potential predictor of acute chest syndrome during vaso‐occlusive crisis in children with sickle cell disease: Exploratory prospective prognostic accuracy study

“…Increased IL-6 levels in sputum might reflect the recruitment of innate immune cells, including monocytes, in the lungs. Indeed, the main chemokine found in sputum during ACS is monocyte-chemoattractantprotein-1 (MCP1), 3 and monocyte stimulation by free HbS was recently shown to induce a predominant increase in IL-6 production mediated by TLR4. 6 In our study, hemoglobin level was negatively correlated with sputum IL-6 level, which supports the hypothesis of a role for hemolysis, leading to the release of free HbS and heme, in ACS pathophysiology.…”