Intrauterine Undernourishment Alters TH1/TH2 Cytokine Balance and Attenuates Lung Allergic Inflammation in Wistar Rats

Abstract

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-gamma is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-alpha and IL-1 beta expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-gamma and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio. Copyright (C) 2012 S. Karger AG, BaselConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Auxilio aos Docentes e Alunos (FADA-UNIFESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Transplantes, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, BR-09972270 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nefrol, Lab Imunol Clin & Expt, BR-09972270 São Paulo, BrazilFAPESP: 07/07139-3FAPESP: 09/09849-3FAPESP: 09/52119-6FAPESP: 10/01404-0FAPESP: 12/02270-2Web of Scienc