Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony‐stimulating factor associated with the acute chest syndrome in patients with sickle cell disease

Abstract

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL‐8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL‐8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso‐occlusive crises. The differences in mean IL‐8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0·0001 and 0·04 respectively). The mean IL‐8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 ± 1400 pg/ml vs. 1900 ± 470 pg/ml, P = 0·03). Granulocyte colony‐stimulating factor (G‐CSF) (2000 ± 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL‐8 and other chemokines. These findings suggest that IL‐8 and G‐CSF may play a role in the development of the ACS and the complications associated with it.

Impact of acute chest syndrome on lung function of children with sickle cell disease

“…A significant association between ACS episodes and asthma has been documented in several studies, [17][18][19] but no study has documented the timing of the asthma diagnosis. The relationship could be explained by the increased release of inflammatory mediators and vascular leak occurring during an ACS episode, 20 increasing AHR and hence asthma. Alternatively, inflammatory mediators and oxidant species produced during an asthma exacerbation 21,22 might increase the expression of adhesion molecules 23 and hence facilitate the adhesion of erythrocytes to the vascular endothelium, 24,25 resulting in a vaso-occlusive crisis.…”

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

“…Investigations of cytokine levels during acute SCD-related complications have shown increased neutrophil chemotaxis, monocyte phagocytosis and levels of IL6 and TNF during VOC (Graido-Gonzalez et al, 1998;Pathare et al, 2004). Additionally, circulating and bronchoalveolar lavage fluid levels of IL8 are elevated in SCD patients with ACS compared to SCD patients at steady state and non-SCD patients (Abboud et al, 2000). However, the immunological processes that occur during various SCD complications make it difficult to ascertain why ACS and VOC may be associated with significantly higher alloimmunization rates than other acute SCD-related complications.…”

How I treat acute chest syndrome in children with sickle cell disease

“…Provision of Duffy antigen by transfusion may attenuate the inflammatory response associated with ACS by binding chemokines, notably IL-8, via the Duffy antigen receptor for chemokines. 85,86 Duffy antigen is both an inflammatory modulator and the entry portal to the red cell by malarial parasites. 87 The latter role has made Duffy antigen positivity extremely rare in West Africa; approximately 70% of African Americans are Duffy antigen negative.…”

“…86 White patients, who in most U.S. centers constitute the majority of blood donors, generally are positive for FYa and/or FYb, 86 and it is speculated that transfusion of Duffy-positive blood may favorably attenuate the course of ACS by its impact on chemokines. 85 Although no supportive clinical data are yet available, extended cross-matching to exclude Duffy incompatibility may be counterproductive, at least regarding treatment of ACS. Extended cross-matching to avoid incompatibility with antigens C, E, and Kell (in addition to D, A, and B) should be performed 88 ; it reduces risk of alloimmunization and is not a major challenge for the blood bank, particularly because most white patients who are D-negative are also C-and E-negative.…”