50 Years Ago in The Journal of Pediatrics: Nutrition and Infection

Abstract

Dubos RJ, Schaedler RW. J Pediatr 1959;55:1-14This lucid, seminal work triggered research that defined the interactions between infection, nutritional status, and host defenses. Observations in India, Africa, and Central America illustrated that when infected, children ate less, lost more nutrients via urine/stools, and stopped growing. The nutrition/infection relationship was conceptualized as a triangle in which diet and infection defined nutritional status, whereas nutrition affected case fatality from infection. The effects of retinol, ascorbate, tocopherol, iron, zinc, copper, and other essential nutrients on innate and acquired defense systems were soon recognized. The epidemiologic and laboratory work of Scrimshaw and Mata in Central America, Chandra in India, and Beisel and Good in the United States, among other researchers, established the critical role of protein-energy malnutrition in defining cellular and humoral immune function as well as nonspecific defenses. Methodological advances facilitated the study of cellular and molecular mechanisms underlying the initial observations in malnourished infants. Thus, the relationship between nutrition and infection expanded to include immunity and the myriad of effects mediated by tissue and circulating cytokines, setting the stage for new layers of complexity in this interaction. Traditional essential nutrients such as tocopherol, retinol, and zinc serve as key regulators of inflammation; arachidonic and eicosapentaenoic acids derived from essential fatty acids were found to mediate immunity, inflammation, and cell injury responses by generating eicosanoids and docosanoids.The chain of interactive events presently includes nutrition, infection, immunity, inflammation, and cell injury. We now acknowledge that nutrient excess as well as deficit can interfere with normal host defense systems. When given in excess, α-tocopherol, a key antioxidant required for normal host defenses, interferes with superoxide production, compromising leukocyte-killing capacity and leading to increased mortality from necrotizing enterocolitis in neonates and pneumonia in older age groups. The role of nutrients in modifying pathogens such as viral agents is also recognized; for example, tocopherol and selenium deficiency in the host increases mutation rates of RNA viruses, leading to progressive increases in virulence of the virus and lethality of subjects further along the expansion of the infection.1Solomons N.W. Malnutrition and infection: an update.Br J Nutr. 2007; 98: S5-S10Crossref PubMed Scopus (53) Google Scholar, 2Katona R. Katona-Apte J. The interaction between nutrition and infection.Clin Infect Dis. 2005; 46: 1582-1588Crossref Scopus (480) Google Scholar More is yet to come in the next 50 years… Dubos RJ, Schaedler RW. J Pediatr 1959;55:1-14 This lucid, seminal work triggered research that defined the interactions between infection, nutritional status, and host defenses. Observations in India, Africa, and Central America illustrated that when infected, children ate less, lost more nutrients via urine/stools, and stopped growing. The nutrition/infection relationship was conceptualized as a triangle in which diet and infection defined nutritional status, whereas nutrition affected case fatality from infection. The effects of retinol, ascorbate, tocopherol, iron, zinc, copper, and other essential nutrients on innate and acquired defense systems were soon recognized. The epidemiologic and laboratory work of Scrimshaw and Mata in Central America, Chandra in India, and Beisel and Good in the United States, among other researchers, established the critical role of protein-energy malnutrition in defining cellular and humoral immune function as well as nonspecific defenses. Methodological advances facilitated the study of cellular and molecular mechanisms underlying the initial observations in malnourished infants. Thus, the relationship between nutrition and infection expanded to include immunity and the myriad of effects mediated by tissue and circulating cytokines, setting the stage for new layers of complexity in this interaction. Traditional essential nutrients such as tocopherol, retinol, and zinc serve as key regulators of inflammation; arachidonic and eicosapentaenoic acids derived from essential fatty acids were found to mediate immunity, inflammation, and cell injury responses by generating eicosanoids and docosanoids. The chain of interactive events presently includes nutrition, infection, immunity, inflammation, and cell injury. We now acknowledge that nutrient excess as well as deficit can interfere with normal host defense systems. When given in excess, α-tocopherol, a key antioxidant required for normal host defenses, interferes with superoxide production, compromising leukocyte-killing capacity and leading to increased mortality from necrotizing enterocolitis in neonates and pneumonia in older age groups. The role of nutrients in modifying pathogens such as viral agents is also recognized; for example, tocopherol and selenium deficiency in the host increases mutation rates of RNA viruses, leading to progressive increases in virulence of the virus and lethality of subjects further along the expansion of the infection.1Solomons N.W. Malnutrition and infection: an update.Br J Nutr. 2007; 98: S5-S10Crossref PubMed Scopus (53) Google Scholar, 2Katona R. Katona-Apte J. The interaction between nutrition and infection.Clin Infect Dis. 2005; 46: 1582-1588Crossref Scopus (480) Google Scholar More is yet to come in the next 50 years…