Sepsis is a runaway inflammatory event resulting from infection, in which the lack of resolution to the inflammatory response leads to organ damage and death. One of the lasting consequences for survivors is a suppression of the immune system's effectiveness, and in today's open access paper researchers draw parallels between this state and the natural aging of the immune system leading to immunosenescence, a loss of the capacity to destroy pathogens and errant cells alike.
Aging does make sepsis worse. The immune system is already in a state of chronic inflammation as a result of the damage of aging: pro-inflammatory secretions of senescent cells, molecular debris from dying or stressed cells that immune cells take for evidence of an attack, and so forth. It is thus less resilient, more susceptible to entering a runaway cytokine storm of the sort provoked in sepsis. Further, because the aged immune system is also less capable, immunosenescent, the suppression of its effectiveness following sepsis can be that much worse, and, further, it is less capable of clearing dangerous infectious agents before they can replicate to the point of causing sepsis.
Sepsis is an intricate, heterogeneous, and highly fatal syndrome, which is responsible for life-threatening organ dysfunction due to the immune regulation disorder. The third international consensus definition of sepsis and septic shock (Sepsis 3.0) recommended the sequential organ failure assessment (SOFA) to assess sepsis and hence predict the subsequent prognosis. While the old definitions of sepsis greatly emphasized infection, Sepsis 3.0 focused on the dysregulation of the body's response to infection and organ dysfunction. Furthermore, the organ damage scored by SOFA focuses on organs like lungs, heart, liver, kidneys, and brain. Surviving sepsis is associated with chronic, long-term consequences in host protective immunity. Additionally, researchers observed that most of the survivors suffered from issues like nervous system disturbances and cognitive dysfunction throughout their life span.
Since several similarities are found between immunosuppression after sepsis and immunosenescence, researchers hypothesized that these two factors might be associated with the progressive failure of immune functions. In sepsis, an increase in the number of myeloid-derived suppressor cells (MDSCs) was associated with the regulation of the function of other immune cells, and excessive inflammation was blocked. It has been suggested that MDSCs play a paradoxical role in sepsis: these cells may increase the production of proinflammatory cytokines during emergency myelogenesis and be also potently immunosuppressive. MDSCs may induce immunosenescence in the remodeled immune system. Therefore, we were interested in analyzing the effect of immunosenescence on sepsis, including the effect on the parenchymal organs. Here we review the possible relationship between septic injury-related organs and immunosenescence and analyze the possible mechanisms of immunosenescence after sepsis, which may shed some light on the delayed consequences of sepsis.