Glucocorticoid dysfunction in children with severe malaria

Introduction Malaria remains a widespread health problem with huge burden. Severe or complicated malaria is highly lethal and encompasses variety of pathological processes, including immune activation, inflammation, dysmetabolism. Previously, we showed that adrenal hormones, in particular glucocorticoids (GCs), play critical roles to maintain disease tolerance during Plasmodium infection mice. Here, GC responses were studied Cameroon children uncomplicated (UM), severe (SM) asymptomatic controls (AC). Methods To determine the sensitivity leukocytes signaling on transcriptional level, measured ex vivo induction glucocorticoid induced leucine zipper (GILZ) FK506-binding protein 5 (FKBP5) by GCs human murine leukocytes. Targeted tracer metabolomics peripheral blood mononuclear cells (PBMCs) was performed detect metabolic changes GCs. Results Total cortisol levels increased patients clinical compared AC higher SM versus UM group, while binding globulin unchanged adrenocorticotropic hormone (ACTH) heterogeneous. Induction both GILZ FKBP5 significantly reduced malaria-infected mice uninfected controls. Increased activity pentose phosphate pathway found patients, but this not affected stimulation physiological hydrocortisone. Interestingly, hydrocortisone cAMP AC, patients. Discussion Altogether, study shows have levels, also decreased GCs, which may clearly contribute severity disease.