Amelioration of experimental colitis after short-term therapy with glucocorticoid and its relationship to the induction of different regulatory markers.
The clinical benefits of short-term therapy with glucocorticoids (GC) in patients with inflammatory bowel disease (IBD) are widely known. However, the effects of this treatment towards the re-establishment of the regulatory network in IBD are not fully explored. We have evaluated the immunological effects of the abbreviated GC therapy in experimental colitis induced by 3% dextran sulphate sodium in C57BL/6 mice. Treatment with GC improved disease outcome, constrained circulating leucocytes and ameliorated intestinal inflammation. The control of the local inflammatory responses involved a reduction in the expression of interferon-γ and interleukin-1β, associated with augmented mRNA levels of peroxisome proliferator-activated receptors (α and γ) in intestine. Furthermore, there was a reduction of CD4+T cells producing interferon-γ, together with an increased frequency of the putative regulatory population of T cells producing interleukin-10, in spleen. These systemic alterations were accompanied by a decrease in the proliferative potential of splenocytes of mice treated in vivo with GC. Notably, treatment with GC also led to an increase in the frequency of the regulatory markers GITR, CTLA-4, PD-1, CD73 and FoxP3, more prominently in spleen. Taken together, our results pointed to a role of GC in the control of leucocyte responsiveness and re-establishment of a regulatory system, which probably contributed to disease control and the restoration of immune balance. Finally, this is the first time that GC treatment was associated with the modulation of a broad number of regulatory markers in an experimental model of colitis.
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Helioswilton
H
Sales-Campos
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Patrícia R
PR
de Souza
Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Paulo J
PJ
Basso
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Viviani
V
Nardini
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Angelica
A
Silva
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Fernanda
F
Banquieri
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Vanessa B F
VB
Alves
Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Brazil.
Javier E L
JE
Chica
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Auro
A
Nomizo
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas - Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Cristina R B
CR
Cardoso
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D002985:Clinical Protocols; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D016264:Dextran Sulfate; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D056747:Immunomodulation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D053450:Glucocorticoid-Induced TNFR-Related Protein; D005938:Glucocorticoids; D053583:Interleukin-1beta; D047492:Peroxisome Proliferator-Activated Receptors; C106544:Tnfrsf18 protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma; D016264:Dextran Sulfate
dextran sulphate sodium-induced colitis; glucocorticoids; immune regulation; inflammatory bowel disease; regulatory cells