CD is a chronic intestinal inflammatory disease with unclear etiology and pathogenesis [1, 3]. Currently, it is believed that genetic, environmental and immune factors are involved in the pathogenesis of CD [3, 25]. The excessive activation and imbalance of immune response may be the most direct and important factor. Activation of the immune system in CD patients will cause immune cells to release immune factors, and inflammatory cells in the mucosa of the intestine will synthesize and release cytokines, which eventually leads to inflammatory lesions of intestine [7, 8, 26]. Although the final targets of CD reside within intestinal tract, CD may also affect multiple organs throughout the body and cause extra-intestinal manifestations, including the skin, muscles, bones, eyes, liver, and gallbladder, which suggest that other events at a circulatory level will take place in the onset phases of this disease at the same time [14, 15].
Peripheral blood circulation plays a significant role in human circulatory system. It contains a variety of immune cells, which is normally the frontier of defense [22, 23]. Previous report showed that monocytes/macrophages were activated in the lesion area of CD and released cytokines to cause intestinal tissue damage. These cytokines could also induce the aggregation of lymphocytes and neutrophils to produce inflammatory effects [9, 10]. In addition, the cellular compositions in blood of CD patients in western countries also exhibited significantly different compared with healthy people. The number of lymphocytes and basophils were reported decreased previously, and the number of monocytes, neutrophils and eosinophils increased [19]. While another study showed decreased eosinophils and unchanged monocytes in blood of CD patients [20]. In this study, the changes of lymphocytes and monocytes in peripheral blood of CD patients were consistent with one of the above researches. However, the percentage and cell number of neutrophils, eosinophils and basophils had no obvious change. These were different from the results in western populations, which may be due to the different populations according to geographic areas. For all this, these results meant the inflammatory changes in peripheral blood of CD patients.
T cells, as the central link of immune regulation, play an important role in the occurrence and development of diseases, and participate in a variety of immune responses to inflammation. Improper enhancement or weakening of immune responses will cause tissue damage or lasting inflammation [27]. Previous study has showed that the killing effect of CD8+ T cells on intestinal epithelium can trigger intestinal inflammation [28]. Besides, CD4+ T cells could perform different biological functions through characteristic cytokines and different transcription pathways, including promoting inflammation and immune regulation [7, 29]. Interestingly, there was an inversion of the CD4+ T cells/CD8+ T cells ratio in PBMC of CD patients in this study, which was less reported. This could be due to the disorders of balance between inflammatory and regulatory T cells of CD. However, its mechanism is still unknown, which need to further clarify.
Inflammation is an important feature of CD. There is an extensive infiltration of immune cells from lamina propria of intestinal mucosa in CD patients. This leads to increase the levels of IFN-γ, TNF-α, IL-1β and other inflammatory cytokines. All these cytokines are associated with the occurrence and development of intestinal inflammation in CD [1, 30]. In addition, persistent intestinal infection or disorder of intestinal microbes also aggravates the inflammation of CD [31]. It was reported that inflammasomes were involved in host defense responses against pathogens and functioned in multiple inflammatory diseases [24, 32]. In this study, CD patients showed increased level of IL-6 and TNF-α, and the NLRP1 and NLRP3 of CD patients increased much higher than healthy people after LPS stimulation. These results of peripheral blood level also indicated the persistent inflammation of CD.