Basic nutritional investigation Influence of age on the development of immunological lung response in intrauterine undernourishment Maristella A. Landgraf, Ph.D. a,b, *, Richardt G. Landgraf, Ph.D. c , Sonia Jancar c , and Zuleica B. Fortes, Ph.D. a a Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil b Department of Health, Centro Universitário Nove de Julho UNINOVE, São Paulo, Brazil c Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil Manuscript received July 6, 2007; accepted December 2, 2007. Abstract Objective: We investigated the effect of intrauterine undernourishment on some features of asthma using a model of allergic lung inflammation in rats. The effects of age at which the rats were challenged (5 and 9 wk) were also evaluated. Methods: Intrauterine undernourished offspring were obtained from dams that were fed 50% of the nourished diet of counterparts and were immunized at 5 and 9 wk of age. They were tested for immunoglobulin E anti-ova titers (by passive cutaneous anaphylaxis), cell count in the bronchoal- veolar fluid, leukotriene concentration, airway reactivity, mucus production, and blood corticoste- rone and leptin concentrations 21 d after immunologic challenge. Results: Intrauterine undernourishment significantly reduced the antigen-specific immunoglobulin E production, inflammatory cell infiltration into airways, mucus secretion, and production of leukotrienes B 4 /C 4 in the lungs in both age groups compared with respective nourished rats. The increased reactivity to methacholine that follows antigen challenge was not affected by intrauterine undernourishment. Corticosterone levels increased with age in the undernourished rats’ offspring, but not in the nourished rats’ offspring. Undernourished offspring already presented high levels of corticosterone before inflammatory stimulus and were not modified by antigen challenge. Leptin levels increased with challenge in the nourished rats but not in the undernourished rats and could not be related to corticosterone levels in the undernourished rats. Conclusion: Intrauterine undernourishment has a striking and age-dependent effect on the off- spring, reducing lung allergic inflammation. © 2008 Elsevier Inc. All rights reserved. Keywords: Asthma; Intrauterine undernutrition; Inflammation; Corticosterone; Leptin Introduction Barker et al. [1] proposed that many chronic diseases arise from adaptations of the fetus when it is undernour- ished. According to this hypothesis, any human fetus has to adapt to a limited supply of nutrients. In doing so, it per- manently changes its structure and metabolism. These “pro- grammed” changes may affect the immune system. It is commonly accepted that inadequate nutrition affects the immune response based on the observation that protein– calorie malnutrition is generally associated with increased susceptibility to infections [2]. Rothman et al. [3] demon- strated that acute starvation may place newborns at in- creased risk of infections and allergic disease and Favennec et al. [4] demonstrated an increased incidence of rhinitis in individuals with deficiency of zinc, vitamin C, and magne- sium. Epidemiologic studies have indicated that, in humans, the incidence of chronic lung disease and alterations of lung functions can be associated with birth weight and specifi- This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo, the Programa de Apoio a Núcleos de Excelência, the Conselho Nacional de Desenvolvimento Científico e Tecnológico, the Fundação de Apoio à Pesquisa do Estado de São Paulo, and the Conselho Nacional de Pesquisa for financial support. * Corresponding author. Tel.: +55-11-3091-7237; fax: +55-11-3091- 7317. E-mail address: mvitta@usp.br (M. A. Landgraf). Nutrition 24 (2008) 262–269 www.elsevier.com/locate/nut 0899-9007/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2007.12.005