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High-mobility group box 1 (HMGB1) and its natural receptor, Toll-like receptor-4 (TLR4), are involved in various infectious or noninfectious diseases including hemorrhagic shock. HMGB1 neutralizing antibody (anti-HMGB1 monoclonal antibody (mAb)) treatment was shown to alleviate ischemia-reperfusion injury effectively. The aim of this study was to explore whether and by what mechanisms anti-HMGB1 mAb attenuates hemorrhagic shock and resuscitation (HS/R)-induced cardiac injury. Employing rat HS/R models, we found that anti-HMGB1 mAb treatment improved HS/R-induced cardiac function deterioration, attenuated cardiac enzyme elevation, improved ATP loss, and protected cardiac tissue. Anti-HMGB1 mAb also inhibited the production of inflammatory factors interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Moreover, anti-HMGB1 mAb reduced apoptotic responses by suppressing activated caspase-3 and reversing apoptotic gene expression of capase-3, Bax, and Bcl-2 in rat cardiac tissue. Moreover, anti-HMGB1 mAb decreased HS/R-induced HMGB1 and TLR4 expression elevation. We further confirmed that anti-HMGB1 mAb inhibited lipopolysaccharide-activated HGMB1 and TLR4 expression and decreased inflammatory factors IL-1β, IL-6, and TNF-α at the cellular level. It was concluded that anti-HMGB1 mAb treatment protects rats from cardiac injury induced by HS/R, and the beneficial effects may be related to its inhibitory effects on the HMGB1-TLR4 axis.

Many studies point to an association between Helicobacter pylori (H. pylori ) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.