Hyperbaric oxygen therapy reduces the toll-like receptor signaling pathway in multiple organ failures

Purpose: Zymosan-induced generalized inflammation is the only experimental model that reproduces characteristics of human multiple organ dysfunction syndrome (MODS). Toll-like receptors (TLRs) are key components in innate immune responses and their signaling pathway is known to activate target genes such as nuclear factor-κB (NF-κB) and cytokines that are involved in inflammation and immune responses. We previously reported that hyperbaric oxygen (HBO) therapy is effective in the treatment of severe zymosan-induced inflammation in MODS. The aim of this study was to investigate the effect of HBO exposure on TLR2 and TLR4 signal transduction and organ dysfunction during MODS induced by zymosan in the rat. Methods: Male Wistar rats were randomized into four groups and treated as follows: (1) saline solution (control); (2) zymosan; (3) HBO 4 and 11 h after zymosan injection; (4) HBO 4 and 11 h after saline solution injection. Zymosan-induced damage of the lungs, liver, and small intestine was evaluated using histology and biochemistry. The activation of the TLR signaling pathway was measured with Western blot, reverse transcriptase polymerase chain reaction analysis (RT-PCR), and immunohistochemistry. Results: Zymosan induced a severe inflammatory response characterized by the activation of the TLR signaling pathway and by an organ dysfunction. HBO exposure significantly reduced the development of lung, liver, and intestine injury in our experimental model. It also significantly reduced the zymosan-induced expression of TLR2 and TLR4, NF-κB activation, and cytokine production. Conclusions: Taken together, these results suggest that, by interfering with the TLR pathway, HBO treatment may exert a protective effect against tissue injury caused by zymosan-induced generalized inflammation.