1. ¹The Pediatric Clinic, The University Hospital Rigshospitalet, Copenhagen, Denmark
2. ²The Medical Faculty, The Institute of Gynecology, Obstetrics, and Pediatrics, The University of Copenhagen, Copenhagen, Denmark
3. ³Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark

Correspondence: Professor K Schmiegelow, The Pediatric Clinic, JMC-5704, University Hospital Rigshopspitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail: kschmiegelow@rh.dk

Abstract

The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations - the adrenal hypothesis - that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus–pituitary–adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets that dominate in the first 5–7 years of life and may furthermore suppress the Th1-dominated proinflammatory response to infections, and thus lower the proliferative stress on pre-existing preleukemic cells.