Proinflammatory cytokines and sepsis syndrome: not enough, or too much of a good thing?

Accumulating data suggest that deficiencies in the production of proinflammatory cytokines result in defective activation of the host defense against invading pathogens, and are associated with an increased susceptibility to infections. In this Opinion, we challenge the view that overproduction of proinflammatory cytokines is a major mechanism in the susceptibility to septic shock. By contrast, we propose that innate deficiency in cytokine release during acute severe infections leads to a rapid multiplication of the invading microorganism, leading to a secondary reaction of the host consisting of systemic inflammatory and anti-inflammatory reactions [systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS)], which could ultimately lead to shock and death. In addition, cytokine deficiencies also contribute to susceptibility to infections in some the patients with recurrent or rare infections.