Hyporesponsiveness in leukocytes in sepsis:: in vitro models reveal paradoxical effects of IL-10

Sepsis syndrome is linked with a systemic inflammatory response syndrome (SIRS). This severe inflammation is associated with an immune suppression as illustrated by the reduced capacity of circulating leukocytes to produce cytokines in response to in vitro activation. Non-infectious SIRS such as trauma, burn, hemorrhage or major surgery is also associated with a suppression of the immune system. This phenomenon has been recently termed CARS for compensatory anti-inflammatory response syndrome. We report in vitro experiments which suggest that a well-known anti-inflammatory cytokine, namely IL-10, may, in certain experimental conditions, prime the leukocytes finally leading to an increased cytokine production. We discuss the relevance of this in vitro model to the in vivo situations where immune suppression is limited to the blood compartment (or the hematopoietic organs) whereas, in inflammatory foci within the tissues, cytokine production is increased. Our data suggest that IL-IO may be a causative agent of concomitantly occurring SIRS and CARS.