ABSTRACT
Acute and chronic pancreatitis are most common gastrointestinal diseases.Recently,there are emerging evidences that immune cell play important roles in the pathogenesis of acute and chronic pancreatitis.Studies have shown that macrophages,high mobility group protein 1 (HMGB 1) and interleukin-33 (IL-33) play an important role in the pathological process of pancreatitis,and are regulated by multiple levels.For example,immune cells are critical in the development and progression of pancreatitis,which not only have the ability to induce microenvironment,but also respond to danger signals derived from endogenous and exogenous molecules.Therefore,further understanding of relevant immune signaling will provide new idea and potential therapeutic targets that can prevent disease progression.Here,we review recent data from animal and human clinical studies that focus on immune responses.
ABSTRACT
<p><b>BACKGROUND</b>Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia). However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.</p><p><b>METHODS</b>Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection) while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment) for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05) and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05). Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.</p><p><b>CONCLUSIONS</b>Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after alemtuzumab treatment.</p>