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* Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany;
Institute of General Practice, Hannover Medical School, Hannover, Germany;
Immunology Division, Walter and Eliza Hall Institute for Medical Research, Melbourne, Australia;
Department of Internal Medicine I, University Hospital of Regensburg, Regensburg, Germany;
¶ Probiodrug, Halle (Saale), Germany;
|| Clinic for Cardiology and Angiology, Hannover Medical School, Hannover, Germany;
# Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany; and
** Experimental Therapy, Franz-Pentzoldt Center, Friedrich-Alexander University, Erlangen, Germany
Genetic and hygienic factors influence susceptibility to asthma. In autoimmune and inflammatory diseases, additional effects of the psychosocial environment have been demonstrated that might also play a role in asthma. In this study, the impact of different early postnatal stressors on an OVA-induced model of asthma was tested in adulthood. Fischer 344 rats were subjected to either repeated handling stimulation (HA), maternal separation (MS), or were left undisturbed in their first 4 wk of life. Behavioral differences were characterized at the age of 4 mo. At 5 mo of age, immunological cellular and serologic changes were investigated and experimental asthma was induced. Results show significantly increased exploratory behavior and reduced anxiety in HA rats compared with MS and controls. Without further behavioral or immunological challenges, HA animals exhibited an increased ex vivo NK cell cytotoxicity but no other obvious immunological differences. After induction of asthma, in contrast, MS animals exhibited proinflammatory effects in leukocyte subset composition including increased eosinophil numbers, whereas levels of IgE and the allergy-specific cytokine IL-13 were reduced compared with HA. There was a most remarkable increase of adrenocorticotropin in HA animals, comparing pre- to postchallenge plasma levels. These data demonstrate for the first time that early postnatal stimulative or adverse experiences exert long-lasting changes of the "neuroendocrinoimmune" interface in adulthood, resulting in either protective or aggravating mechanisms in allergic airway disease. Thus, in addition to genetic and hygienic factors, nongenetically acquired individual differences contribute to the pathobiology of asthma.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft), SFB587, Project B11.
2 Address correspondence and reprint requests to Dr. Stephan von Hörsten, Experimental Therapy, Franz-Pentzoldt Center, Friedrich-Alexander University, 91054 Erlangen, Germany. E-mail address: stephan.v.hoersten{at}ze.uni-erlangen.de
3 Abbreviations used in this paper: MS, maternal stimulation; HA, handling stimulation; CO, control; HPA, hypothalamic-pituitary-adrenal; SI, social interaction; i.t., intratracheal; ACTH, adrenocorticotropin; BAL, bronchoalveolar lavage.
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