A 23-year-old man is referred to the gastroenterology clinic due to a 3-year history of recurring abdominal pain accompanied by cramps and diarrhea. The patient has noticed an increased frequency of episodes lately with worsening pain. He also says that his urine occasionally appears dark brown and his urine stream sometimes sputters. Imaging studies reveal a colovesical fistula. Biopsy obtained during colonoscopy shows chronic ileocolitis with discontinuous transmural inflammation and noncaseating granulomas. When given the diagnosis of Crohn disease, the patient becomes skeptical and says, "There's no way I'm getting a colostomy bag." He then refuses treatment and pursues a second opinion once his symptoms subside. A second biopsy demonstrates reduced inflammation in regions of previously active ileocolitis. An increase in which of the following cytokines is most likely responsible for this patient's clinical regression?

Question

A 23-year-old man is referred to the gastroenterology clinic due to a 3-year history of recurring abdominal pain accompanied by cramps and diarrhea.  The patient has noticed an increased frequency of episodes lately with worsening pain.  He also says that his urine occasionally appears dark brown and his urine stream sometimes sputters.  Imaging studies reveal a colovesical fistula.  Biopsy obtained during colonoscopy shows chronic ileocolitis with discontinuous transmural inflammation and noncaseating granulomas.  When given the diagnosis of Crohn disease, the patient becomes skeptical and says, "There's no way I'm getting a colostomy bag."  He then refuses treatment and pursues a second opinion once his symptoms subside.  A second biopsy demonstrates reduced inflammation in regions of previously active ileocolitis.  An increase in which of the following cytokines is most likely responsible for this patient's clinical regression?

Quizplus · Accepted Answer

11ec160b_37cb_3c2e_9249_c73f38deb2ba_MD0001_00 The balance of pro- and anti-inflammatory cytokines in the intestinal mucosa is essential for homeostasis. Overproduction of proinflammatory cytokines leads to pathology such as that observed in inflammatory bowel diseases. Among the listed choices, IL-10 is the only cytokine with anti-inflammatory properties. IL-10 reduces production of proinflammatory T_H1 cytokines (IL-2 and interferon gamma) and major histocompatibility complex class II expression (important for antigen presentation and T-helper cell response). It also inhibits activated dendritic cells and macrophages. These effects of IL-10 result in the attenuation of cellular-mediated immunity with some enhancement of the humoral response, leading to a protective effect in Crohn disease. (Choice A) IL-1, produced by macrophages and epithelial cells, has proinflammatory properties such as endothelium activation, increased chemokine expression (promoting leukocyte recruitment), and induction of fever. IL-1β is important for differentiation of T_H17 cells. (Choice B) IL-5 is secreted by T_H2 cells and promotes the humoral response by stimulating differentiation of B cells and increasing IgA production. It also promotes the growth and differentiation of eosinophils and is implicated in the pathogenesis of many allergic diseases (eg, asthma). (Choice D) IL-12 is secreted by macrophages and induces differentiation of T_H1 cells and activation of natural killer cells. (Choice E) Interferon gamma is secreted by T_H1 cells and promotes proinflammatory pathways by activating macrophages, increasing antigen presentation, and inducing the death of epithelial cells. (Choice F) Tumor necrosis factor-alpha, produced by macrophages, natural killer cells, and T cells, is a proinflammatory mediator that promotes leukocyte recruitment and activates the endothelium (increases expression of adhesion molecules). Educational objective: Of the cytokines released in the setting of tissue injury, IL-10 plays important anti-inflammatory and immunomodulatory roles, especially in the pathogenesis of inflammatory bowel disease. IL-10 attenuates the immune response through the inhibition of T_H1 cytokines, reduction of major histocompatibility complex class II expression, and suppression of activated macrophages and dendritic cells. __________ References: Role of cytokines in inflammatory bowel disease. (http://www.ncbi.nlm.nih.gov/pubmed/18666314) Recent advances in cytokines: therapeutic implications for inflammatory bowel diseases. (http://www.ncbi.nlm.nih.gov/pubmed/21350703)

A 23-Year-Old Man Is Referred to the Gastroenterology Clinic Due