Inflammatory bowel disease (IBD) is comprised of Crohn’s disease and ulcerative colitis, both chronic inflammatory intestinal disorders of unknown etiology characterized by a waxing and waning clinical cou...Inflammatory bowel disease (IBD) is comprised of Crohn’s disease and ulcerative colitis, both chronic inflammatory intestinal disorders of unknown etiology characterized by a waxing and waning clinical course. For many years, the drug therapy was limited to sulfasalazine and related aminosalicylates, corticosteroids and antibiotics. Studies suggesting that the pathophysiology of these disorders relates to a disregulated, over-active immune response to indigenous bacteria have led to the increasing importance of immunosuppressive drugs for the therapy of IBD. This review details the mechanisms of action, clinical efficacy, and adverse effects of these agents.展开更多
In the last decades,with the development of biological therapy,the treatment paradigms in patients with Crohn＇s disease have continuously evolved.Several studies focusing on the optimal use of both traditional immuno...In the last decades,with the development of biological therapy,the treatment paradigms in patients with Crohn＇s disease have continuously evolved.Several studies focusing on the optimal use of both traditional immunosuppressants and biological therapy have been published,investigating conventional,accelerated stepup and top-down approaches.In addition,much emphasis has been placed in recent years on the de-termination of important predictive factors that could enable early patient stratification,which would lead to a tailored management strategy.In this review,the authors try to highlight new evidence on the optimal timing,benefits,and risks of immunosupressants alone,or in combination,in patients with Crohn＇s disease.展开更多
Acute pancreatitis(AP) is a common disease,which usually exists in its mild form.However,in a fifth of cases,the disease is severe,with local pancreatic complications or systemic organ dysfunction or both.Because the ...Acute pancreatitis(AP) is a common disease,which usually exists in its mild form.However,in a fifth of cases,the disease is severe,with local pancreatic complications or systemic organ dysfunction or both.Because the development of organ failure is the major cause of death in AP,early identification of patients likely to develop organ failure is important.AP is initiated by intracellular activation of pancreatic proenzymes and autodigestion of the pancreas.Destruction of the pancreatic parenchyma first induces an inflammatory reaction locally,but may lead to overwhelming systemic production of inflammatory mediators and early organ failure.Concomitantly,anti-inflammatory cytokines and specific cytokine inhibitors are produced.This anti-inflammatory reaction may overcompensate and inhibit the immune response,rendering the host at risk of systemic infection.At present,there is no specific treatment for AP.Increased understanding of the pathogenesis of systemic inflammation and development of organ dysfunction may provide us with drugs to ameliorate physiological disturbances.展开更多
Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immuno...Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.展开更多
文摘Inflammatory bowel disease (IBD) is comprised of Crohn’s disease and ulcerative colitis, both chronic inflammatory intestinal disorders of unknown etiology characterized by a waxing and waning clinical course. For many years, the drug therapy was limited to sulfasalazine and related aminosalicylates, corticosteroids and antibiotics. Studies suggesting that the pathophysiology of these disorders relates to a disregulated, over-active immune response to indigenous bacteria have led to the increasing importance of immunosuppressive drugs for the therapy of IBD. This review details the mechanisms of action, clinical efficacy, and adverse effects of these agents.
文摘In the last decades,with the development of biological therapy,the treatment paradigms in patients with Crohn＇s disease have continuously evolved.Several studies focusing on the optimal use of both traditional immunosuppressants and biological therapy have been published,investigating conventional,accelerated stepup and top-down approaches.In addition,much emphasis has been placed in recent years on the de-termination of important predictive factors that could enable early patient stratification,which would lead to a tailored management strategy.In this review,the authors try to highlight new evidence on the optimal timing,benefits,and risks of immunosupressants alone,or in combination,in patients with Crohn＇s disease.
文摘Acute pancreatitis(AP) is a common disease,which usually exists in its mild form.However,in a fifth of cases,the disease is severe,with local pancreatic complications or systemic organ dysfunction or both.Because the development of organ failure is the major cause of death in AP,early identification of patients likely to develop organ failure is important.AP is initiated by intracellular activation of pancreatic proenzymes and autodigestion of the pancreas.Destruction of the pancreatic parenchyma first induces an inflammatory reaction locally,but may lead to overwhelming systemic production of inflammatory mediators and early organ failure.Concomitantly,anti-inflammatory cytokines and specific cytokine inhibitors are produced.This anti-inflammatory reaction may overcompensate and inhibit the immune response,rendering the host at risk of systemic infection.At present,there is no specific treatment for AP.Increased understanding of the pathogenesis of systemic inflammation and development of organ dysfunction may provide us with drugs to ameliorate physiological disturbances.
文摘Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.
