Plasma and sputum levels of the main proinflammatory cytokines and chemokines in children with SCD. (A) Plasma level of IL-6 in 9 healthy controls and 36 SCD patients, at steady state (n = 12), during VOC (n = 12), and during ACS (n = 12). Median (IQR) plasma IL-6 level was not significantly higher during ACS (49 [37-94] pg/mL) compared with during VOC (54 [52-72] pg/mL), at steady state (36 [27-50] pg/mL), and in controls (36 [28-43] pg/mL). (B) By contrast, median (IQR) IL-6 level in sputum was dramatically elevated (3320 [1233-6459] pg/mL) in SCD patients during ACS (n = 12) compared with non-ACS (n = 6) respiratory events (13 [11-19] pg/mL; P = .0009). (C) For the 5 patients who had concomitant sputum and plasma collections during ACS, median (IQR) IL-6 level was >150-fold higher in sputum (6892 [6314-7114] pg/mL) than in plasma (42 [35-48] pg/mL; P = .0009). (D,F) Median plasma IL-1β and TNF-α levels were not increased during ACS compared with during VOC, at steady state, and in controls. (E,G) Median levels of IL-1β and TNF-α in sputum were not significantly increased during ACS compared with non-ACS respiratory events. (H-J) Median (IQR) sputum chemokine levels were higher during ACS compared with non-ACS respiratory events for IL-8 (3632 [1121-11 976] pg/mL vs 774 [575-948] pg/mL; P = .044) (H), CCL2 (591 [263-1624] pg/mL vs 37 [30-46] pg/mL; P = .0009) (I), and CCL3 (62 [32-105] pg/mL vs 12 [9-19] pg/mL; P = .01) (J). *P < .05, ***P < .001.