Amelioration of experimental colitis after short‐term therapy with glucocorticoid and its relationship to the induction of different regulatory markers

Abstract

Summary 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.

Morinda citrifolia(Noni) Fruit Juice Reduces Inflammatory Cytokines Expression and Contributes to the Maintenance of Intestinal Mucosal Integrity in DSS Experimental Colitis

“…Therefore, therapies aiming to reduce this cytokine might be helpful in controlling inflammation and improving disease outcome. In this context, a short-term glucocorticoid treatment of mice exposed to DSS for six days was able to reduce the frequency of IFN- γ -producing CD4 + cells in the spleen and to decrease the expression of this cytokine and IL-1 β in the intestine [ 49 ]. This reduction in the activity of IFN- γ was followed by an improvement in the clinical outcome and restoration of immune balance [ 49 ].…”

“…In this context, a short-term glucocorticoid treatment of mice exposed to DSS for six days was able to reduce the frequency of IFN- γ -producing CD4 + cells in the spleen and to decrease the expression of this cytokine and IL-1 β in the intestine [ 49 ]. This reduction in the activity of IFN- γ was followed by an improvement in the clinical outcome and restoration of immune balance [ 49 ]. Additionally, the beneficial effects associated with the reduction of inflammatory cytokines such as IL-1 β and IFN- γ were further elucidated in a murine model of colitis.…”

Prednisone may induce immunologic tolerance by activating the functions of decidual immune cells in early pregnancy

“…This immune suppression requires sustained FOXP3 expression, which is tightly regulated by STAT5 [ 10 ]. Glucocorticoid treatment increases the proportion of Treg cells and of related regulatory markers such as GITR, CTLA-4, PD-1, CD73 and FOXP3 [ 16 ]. In the present study, treating first-trimester DICs with prednisone up-regulated STAT5, which in turn induced expression of FOXP3 and IL-10.…”

Traditional Drugs: Mechanisms of Immunosuppressor and Corticosteroid Therapies for Inflammatory Bowel Diseases

“…In contrast, mice exposed to dextran sodium sulfate for colitis development and treated for short term with the glucocorticoid dexamethasone had decreased intestinal inflammation, with reduced expression of pro-inflammatory cytokines such as IFN-γ and IL-1, diminishment of IFNγ-producing CD4 + T cells and augmented frequency of anti-inflammatory cytokine-producing cells such as IL-10. Moreover, the increase in the frequency of regulatory markers such as GITR, CTLA-4, PD-1, CD73, and FoxP3 in treated mice pointed to a relevant role for this short-term therapy in the induction of immune regulation [19], despite the long-term adverse effects of these drugs. These findings corroborate the relevance of this hormone in the regulation of mucosal immunity.…”