Systemic immune response of burns from the acute to chronic phase

Abstract

Immune responses that occur following burn injury comprise a series of reactions that are activated in response to damaged autologous tissues, followed by removal of damaged tissues and foreign pathogens such as invading bacteria, and tissue repair. These immune responses are considered to be programmed in living organisms. Developments of modern medicine have led to the saving of burned patients who could not be cured previously; however, the programmed response is no longer able to keep up, and various problems have arisen. This paper describes the mechanism of immune response specific to burn injury and the emerging concept of persistent inflammation, immunosuppression, and catabolism syndrome.

Keywords: DAMPs; PAMPs; compensatory anti‐inflammatory response syndrome; persistent inflammation, immunosuppression, and catabolism syndrome; systemic inflammatory response syndrome.

FIGURE 1

Diagram of the immune response following burn injury. A two‐hit response during the SIRS phase leads to inflammatory multiorgan failure. Relatively small burns have a simple outcome of wound closure and healing without complications, but usually have a complex outcome with many complications. After the initial SIRS inflammatory and CARS anti‐inflammatory responses, many patients present with a clinical picture of protein loss, malnutrition, delayed wound healing, and recurrent infections. In addition, there is a persistent inflammatory response and dysfunction of both innate and acquired immunity. Clinically, early complications include TSS, followed by sepsis, fatty liver, and NOMI after about 1 month. Convergence to a state in which both inflammatory and anti‐inflammatory responses are abolished leads to a cure. CARS, compensatory anti‐inflammatory response syndrome; CCI, chronic critical illness; NOMI, non‐obstructive mesenteric ischemia; PIICS, persistent inflammation, immunosuppression, and catabolism syndrome; SIRS, systemic inflammatory response syndrome; TSS, toxic shock syndrome.

FIGURE 2

Immune cell changes following burn injury. DAMPs released from tissue damage such as burn injuries induce inflammation mainly by activating macrophages of the innate immune system. DAMPs activate immunocompetent cells by signaling through PRRs such as TLRs and inflammasomes, which increase the release of multiple inflammatory mediators (IL‐1, IL‐6, IL‐8, IL‐18, TNF‐γ, etc.). At the same time, Lymphocytes responsible for cellular immunity are decreased, but Th2 is increased due to increases in IL‐4 and IL‐10 and decreases in IL‐2 and IFN‐γ. And Tregs of the acquired immune system are also activated to control excessive inflammation. However, when bone marrow‐derived stem cells are rapidly differentiated, they release MDSCs. MDSCs enhance Treg function and suppress macrophage and T‐cell function, leading patients to a state of PIICS. DAMPs, damage‐associated molecular patterns; IFN, interferon; IL‐, interleukin‐; MDSCs, myeloid‐derived suppressor cells; PIICS, persistent inflammation, immunosuppression, and catabolism syndrome; PRRs, pattern recognition receptors; TLRs, toll‐like receptors; TNF‐α, tumor necrosis factor alpha; Tregs, regulatory T cells.