Figure 1: Influence of the sepsis-induced cytokine storm and immunoparalysis state on host immune response.

A) In the first several hours to days following a septic insult, lymphocytes become activated and begin contributing pro-inflammatory cytokines [4–6]. As the infection begins to become mismanaged lymphocytes begin to undergo apoptosis and produce anti-inflammatory cytokines to counterbalance the pro-inflammatory cytokines and limit immunopathology. The culmination of the pro- and anti-inflammatory cytokine responses is termed the cytokine storm. B) If the host survives the cytokine storm, then as the inflammation subsides the host is left with a substantially reduced number of lymphocytes and these surviving lymphocytes exhibit functional impairment. This defines the early immunoparalysis state that may last for days to weeks after the septic insult wherein hosts are now more susceptible to secondary pathogenic insults (i.e., infection or cancer). [8–11] C) With time the number of total lymphocytes recovers, however, these lymphocytes continue to exhibit functional impairment years after the septic insult due to sepsis-induced cell-intrinsic and -extrinsic changes [15]. This defines the late immunoparalysis state that is also associated with increased susceptibility to secondary pathogenic insults.