Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
Inflammatory Response to Hydroxyurea Therapy in Sickle Cell Disease
In sickle cell disease (SCD), polymerisation of haemoglobin S and the resulting shape change
 of the red blood cells (RBC) lead to vascular occlusion and severe painful crises. Permanent
 inflammatory state and abnormal RBC adhesion to the endothelium trigger these phenomenon.
 Hydroxyurea (HU) is the only drug that has been shown to reduce clinical severity of SCD, and
 this was initially attributed to the stimulation of foetal haemoglobin (HbF). However, the
 clinical response does not correlate consistently with the degree and time of HbF increment,
 suggesting that HU clinical benefits may involve other mechanisms such as the induction of
 natural anti-inflammatory response via the hypothalami-pituitary-adrenal axis.
Plasmatic proinflammatory molecules (C-reactive protein, orosomucoid, RANTES, IL-6, IL-8,
 MCP-1, IL-1A, IL-1B, ET-1, IL-4, IL-10, TNFalpha, IFNgamma), hormones from the
 hypothalami-pituitary-adrenal axis (cortisol, ACTH), and hypothalamic peptids (arginine
 vasopressin, corticotrophin-releasing hormone) will be measured from SCD children treated or
 not with HU (20 treated children, 20 untreated children with a history of vaso-occlusive
 events, 20 asymptomatic children, and 20 healthy African controls).
INCLUSION CRITERIA:

 1. Homozygous SS sickle cell children, aged > 3 years, of sub-Saharian Africa extraction,
 in a steady-state of disease (free of any infectious or vaso-occlusive events for the
 4 weeks prior to and 2 weeks after blood sampling, and transfusion-free for 4 months
 prior to blood sampling), taken no drug except penicillin-V, folate or iron
 supplementation, hydroxyurea, divided into three groups :

 -  children treated with hydroxyurea 20-25 mg/kg/day since at least 3 months with
 clinical efficacy on vaso-occlusive events

 -  untreated children with major vaso-occlusive events

 -  children > 5 year-old without a history of vaso-occlusive events Signed informed
 consent obtained from the subjects (if possible) and their parents

 2. Controls : heterozygous AS parents or siblings of the patients, and AA siblings or
 healthy African unrelated subjects, aged > 3 years, taken no drug on the day of blood
 sampling.

 Signed informed consent obtained from the subjects (if possible) and their parents

 EXCLUSION CRITERIA:

 -  Children in a acute-phase of the disease

 -  Parent's or patient's refusal

 -  Taking any drug except penicillin-V, folate or iron supplementation, hydroxyurea

 -  Un-healthy control or taking drug