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

Abstract

1. Sputum interleukin-6 (IL-6) level is high during acute chest syndrome (ACS) in pediatric sickle cell disease, supporting anti–IL-6 trials.

2. Sputum IL-8, CCL2, and CCL3 levels are also high during ACS, possibly contributing to recruitment of inflammatory cells in the lungs.

Figure 1.

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.