High pre-treatment MPV level in IBC patients was a potential predictive factor and significant independent prognostic factor.

Human basophils have been implicated in the pathogenesis of chronic spontaneous urticaria (CSU), and substance P (SP) is a possible candidate as histamine-releasing factor in some patients with CSU. However, little is known of relationship between basophils and SP in CSU. In the present study, we investigated expression of SP and NK1R on basophils from patients with CSU, and influence of SP on basophil functions by using flow cytometry analysis, basophil challenge, and mouse sensitization model techniques. The results showed that plasma SP level and basophil numbers in CSU patients were higher than that in HC subject. The percentages of SP+ and NK1R+ basophils were markedly elevated in CSU blood in comparison with HC blood. Once added, SP induced up to 41.2 % net histamine release from basophils of CSU patients, which was comparable with that provoked by anti-IgE, and fMLP. It appeared that SP induced dramatic increase in blood basophil numbers of mice following peritoneal injection. Ovalbumin (OVA)-sensitized mice had much more SP+ and NK1R+ basophils in blood than non-sensitized mice. In conclusion, the elevated plasma concentration of SP, upregulated expression of SP and NK1R on basophils, and the ability of SP in induction of basophil degranulation and accumulation indicate strongly that SP is most likely a potent proinflammatory mediator, which contributes greatly to the pathogenesis of CSU through basophils. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of CSU.

Previous studies have indicated that regulatory T cells serve essential roles in maintaining intestinal homeostasis, however, the role of different Treg subsets in modulating inflammatory bowel disease has still not been addressed clearly. In the present study, the authors measured the percentage of Foxp3+ IL‑10+ TGF‑β+ natural Tregs, Foxp3‑ IL‑10+ TGF‑β‑ induced Tregs, CD127‑ induced Tregs and CD8+ Tregs at different time points in DSS‑induced experimental colitis model in murine lamina propria lymphocytes, mesenteric lymph node and peripheral blood. In addition, the authors compared the frequency of four Treg subsets in patients diagnosed of ulcerative colitis at different stages with enrolled healthy controls. The percentage of Foxp3+ IL‑10+ TGF‑β+ natural Tregs decreased in acute stage of both human and mice was observed, but proliferated significantly during remittent stage. Foxp3‑ IL‑10+ TGF‑β‑ inducible (i) Treg and CD127‑ iTreg was observed as being significantly decreased percentage in LPL at 4 and 7 days, the frequency of Foxp3‑ IL‑10+ TGF‑β‑ iTreg cells became decreased and CD127‑ iTreg only slightly increased at the chronic stage following DSS induction. However, the proportion of both Foxp3‑ IL‑10+ TGF‑β‑ iTreg and CD127‑ iTreg was nearly unchanged in human IBD. Although intestinal inflammation decreased the percentage of CD8+ Tregs, it remained lower in the remittent stage of human IBD. Only enhanced proliferation of lamina propria lymphocytes‑derived CD8+ Treg was reported at 7 days in dextran sodium sulfate‑induced murine colitis. The results demonstrated that Foxp3+ IL‑10+ TGF‑β+ natural Tregs may serve an essential role in exhibiting suppressive and protecting from immune‑related mucosal injury during chronic stage in inflammatory bowel disease.

Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model. The results showed that plasma SP and IL-17A levels in eczema patients were higher than that in healthy control subject. The percentages of SP+ and NK1R+ expression populations of monocytes, helper T cells, natural killer T cells and basophils in peripheral blood of eczema patients were markedly elevated. It was observed that not only absolute number of mast cells but also SP+ and NK1R+ mast cells are enhanced in the lesion skin of eczema. SP showed a potent chemoattractant action on mast cells as assessed by a mouse peritoneal model and a trans-endothelium cell migration assay. SP-induced mast cell accumulation appears a CD18/CD11a complex, L-selectin and ICAM-1-dependent event which can be blocked by a NK-1R antagonist RP67580. In conclusion, elevated expression of SP in patients with eczema and the ability of SP in induction of mast cell accumulation indicate strongly that SP is a potent proinflammatory mediator, which contributes to the pathogenesis of eczema. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of eczema.