Controlling Gut Inflammation by Restoring Anti-Inflammatory Pathways in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is caused by a dysregulated immune response against normal components of the intestinal microflora combined with defective functioning of anti-inflammatory pathways. Currently, all therapies approved for IBD manipulate the immune system by inhibiting pro-inflammatory mechanisms, such as tumor necrosis factor-α, gut-homing α4β7 integrin, interleukin-12/interleukin-23, and Janus kinases. However, some IBD patients are non-responders to these drugs, which are also associated with serious side effects. Thus, it has been hypothesized that therapies aimed at restoring anti-inflammatory signals, by exploiting the tolerogenic potential of cytokines (interleukin-10, transforming growth factor-β, granulocyte macrophage colony-stimulating factor), immune cells (regulatory T cells, tolerogenic dendritic cells), or mesenchymal stem cells, might offer promising results in terms of clinical efficacy with fewer side effects. In this review, we provide new insights into putative novel treatments aimed at restoring anti-inflammatory signaling pathways in IBD

Defective spleen function in autoimmune gastrointestinal disorders

Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria