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Nutritional Immunology

Higher Serum Concentrations of DHEAS Predict Improved Nutritional Status in Helminth-Infected Children, Adolescents, and Young Adults in Leyte, the Philippines¹

² Center for International Health Research (CIHR), Rhode Island Hospital, Brown University Medical School, Providence, RI 02903; ³ CIHR and Department of Pediatrics, Rhode Island Hospital, Brown University Medical School, Providence, RI 02903; ⁴ Research Institute of Tropical Medicine, FILINVEST Corporate City, Alabang, Muntinlupa City, 1781 Phillipines; ⁵ Epidemiology Section, Department of Community Health and International Health Institute, Brown University, Providence, RI 02912; and ⁶ CIHR and Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Brown University Medical School, Providence, RI 02903

^* To whom correspondence should be addressed. E-mail: h.m.coutinho{at}hetnet.nl or jonathan_kurtis{at}brown.edu.

Pubertal development and associated downmodulation of proinflammatory cytokines may predict improved nutritional status, independent of chronic parasite infections, in developing countries. We enrolled 731 individuals, aged 7–30 y, from Leyte, the Philippines, where helminth infections and nutritional morbidity are highly prevalent. The following data were collected: venous blood hemoglobin and serum concentrations of ferritin, dehydroepiandrosterone sulfate (DHEAS), C-reactive protein and proinflammatory cytokines (IL-1, IL-6, TNF-, and soluble TNF receptor I); anthropometric measurements to calculate upper arm muscle area Z-score and sum of triceps and subscapular skinfolds Z-score; stool samples to determine Schistosoma japonicum and geohelminth egg counts; and responses to questionnaires assessing socio-economic status. In cross-sectional multilevel linear and logistic regression analyses adjusted for confounders, relations were assessed between 1) DHEAS and nutritional status, 2) DHEAS and proinflammatory cytokines, and 3) nutritional status and proinflammatory cytokines. Independent of age, socio-economic status, and helminth infections, increased levels of DHEAS were associated with improved nutritional status and decreased prevalence of non-iron deficiency anemia in both males and females. DHEAS showed dose-dependent inverse associations with C-reactive protein (P = 0.08) and the production of IL-6 (P < 0.0001). These inflammatory markers, in turn, were consistently associated with undernutrition and anemia. The results suggest that the puberty-associated rise in DHEAS downmodulates proinflammatory immune responses and thereby reduces undernutrition and anemia in a population experiencing a high burden of chronic helminth infections. This novel regulatory mechanism of inflammation-related nutritional morbidity emphasizes the importance of treating prepubescent children for helminth infections.

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