This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coe, C. L. Articles by Fuchs, E. Search for Related Content PubMed PubMed Citation Articles by Coe, C. L. Articles by Fuchs, E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DEXAMETHASONE Medline Plus Health Information High Risk Pregnancy Seniors' Health

Prenatal Stress Diminishes the Cytokine Response of Leukocytes to Endotoxin Stimulation in Juvenile Rhesus Monkeys

Division of Neurobiology (M.K., E.F.), German Primate Center, Göttingen D-37077, Germany; Harlow Primate Laboratory (C.L.C.), University of Madison, Madison, Wisconsin 53706; Department of Psychology (C.K.), University of Düsseldorf, 40225 Düsseldorf, Germany; and Department of Psychology (M.K., P.N.), University of Giessen, 35384 Giessen, Germany

Address all correspondence and requests for reprints to: Eberhard Fuchs, Division of Neurobiology, German Primate Center, Kellnerweg 4, D-37077 Göttingen, Germany. E-mail: efuchs{at}gwdg.de

Abstract

This study investigated whether exposing the fetal primate to repeated episodes of maternal stress would have long-lasting effects on the endotoxin-induced cytokine response and corticosteroid sensitivity of peripheral blood cells in juvenile animals. Pregnant rhesus monkeys were acutely aroused on a daily basis for 6 wk using an acoustical startle protocol, either early or late in the 24-wk pregnancy. To quantify cytokine responses and corticosteroid sensitivity in their offspring at 2 yr of age, whole blood cultures were stimulated with lipopolysaccharide and incubated with dexamethasone (DEX). TNF and IL-6 levels were determined in the culture supernatants. The blood samples were collected from undisturbed monkeys under baseline conditions, as well as in an aroused state induced by a 2 h social separation. Juvenile monkeys from stressed pregnancies had significantly lower cellular cytokine responses compared with the undisturbed controls. When DEX was added to the cell cultures, it systematically inhibited TNF and IL-6 production, bringing the values for control animals down into the range of the prenatally stressed animals. Lipopolysaccharide-induced cytokine production was also markedly suppressed by the experience of acute stress, reducing cytokine responses of controls to the levels found for prenatally disturbed monkeys under baseline conditions. Therefore, this study has demonstrated that prenatal disturbance can induce a lasting change in cytokine biology, which persists well beyond the fetal and infant stage. Further, these effects may be due to elevated hypothalamic-pituitary-adrenal activity in the prenatally stressed animals, because both DEX and acute arousal made the cells from control monkeys appear more similar to those from disturbed pregnancies.

This article has been cited by other articles:

				G. N. Neigh, C. F. Gillespie, and C. B. Nemeroff The Neurobiological Toll of Child Abuse and Neglect Trauma Violence Abuse, October 1, 2009; 10(4): 389 - 410. [Abstract] [PDF]

				A. Buske-Kirschbaum, S. Krieger, C. Wilkes, W. Rauh, S. Weiss, and D. H. Hellhammer Hypothalamic-Pituitary-Adrenal Axis Function and the Cellular Immune Response in Former Preterm Children J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3429 - 3435. [Abstract] [Full Text] [PDF]

				M. K. Pincus-Knackstedt, R. A. Joachim, S. M. Blois, A. J. Douglas, A. S. Orsal, B. F. Klapp, U. Wahn, E. Hamelmann, and P. C. Arck Prenatal Stress Enhances Susceptibility of Murine Adult Offspring toward Airway Inflammation J. Immunol., December 15, 2006; 177(12): 8484 - 8492. [Abstract] [Full Text] [PDF]