Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses.
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-у 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 100μM). 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-β 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-ɣ(+) 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.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Vanessa Beatriz Freitas
VB
Alves
Departamento de Imunologia e Bioquímica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Paulo José
PJ
Basso
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Viviani
V
Nardini
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
Angélica
A
Silva
Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Brazil.
Javier Emílio Lazo
JE
Chica
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: cristina@fcfrp.usp.br.
Cristina Ribeiro de Barros
CR
Cardoso
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D003687:Dehydroepiandrosterone / Q000494:pharmacology* / Q000627:therapeutic use; D016264:Dextran Sulfate; D007420:Intestine, Large / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects; D008198:Lymph Nodes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D016264:Dextran Sulfate
Colitis; Dehydroepiandrosterone; Immunomodulation; Inflammatory bowel disease; Mice