Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses

Author(s)

Freitas Alves, Vanessa Beatriz ^[1] ; Basso, Paulo Jose ^[2] ; Nardini, Viviani ^[1] ; Silva, Angelica ^[1] ; Lazo Chica, Javier Emilio ^[3] ; de Barros Cardoso, Cristina Ribeiro ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Imunol & Bioquim, Sao Paulo - Brazil

^[3] Univ Fed Triangulo Mineiro, Inst Ciencias Biol & Nat, Uberaba - Brazil

• Document type: Journal article
• Source: Immunobiology; v. 221, n. 9, p. 934-943, SEP 2016.
• Web of Science Citations: 3

Abstract

Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-y production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at,the intermediate and highest doses in vitro (50 and 100 mu M). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-beta mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-y(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD. (C) 2016 Elsevier GmbH. All rights reserved. (AU)

• FAPESP's process: 10/20162-7 - The role of hypothalamus-pituitary-adrenal (HPA) axis and exogenous glucocorticoids in the modulation of immune response in inflammatory bowel disease
• Grantee: Cristina Ribeiro de Barros Cardoso
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 12/17265-4 - Study of the immunomodulatory potential of Dehydroepiandrosterone (DHEA) in experimental intestinal inflammation
• Grantee: Vanessa Beatriz Freitas Alves
• Support Opportunities: Scholarships in Brazil - Doctorate