Anti-inflammatory cytokine response and the development of multiple organ failure in severe sepsis

Background: The production of proinflammatory cytokines activates the systemic inflammatory response in sepsis. Patients also develop a compensatory anti‐inflammatory reaction, which may have an important down‐regulatory effect on the overactive inflammation. However, the role of this anti‐inflammatory response in sepsis is not completely clarified. In this prospective study, we investigated the relationship between the pro‐ and anti‐inflammatory cytokine profiles in severe sepsis and their role in the development of multiple organ failure (MOF). Methods: Thirty‐eight patients meeting the criteria for severe sepsis were studied. MOF was defined as a maximum SOFA score of 10 or higher. Serial measurements of the proinflammatory IL‐6 and IL‐1β and the anti‐inflammatory IL‐10 and IL‐1ra were used. The cytokine samples were taken at the onset of sepsis and on the third and fifth day during the ICU period. Results: The initial IL‐10 and IL‐1ra responses were identical in patients with or without MOF. The anti‐inflammatory cytokine levels remained elevated in the MOF patients, whereas in patients without MOF the levels declined. The IL‐6/IL‐10 ratio was significantly higher in the MOF patients on days 1 and 3 compared with patients without MOF. Conclusions: We could not demonstrate overproduction of anti‐inflammatory IL‐10 in MOF patients. On the contrary, the high IL‐6/IL‐10 ratio indicates that IL‐10 deficiency may contribute to the development of MOF in severe sepsis.