INCREASED SUSCEPTIBILITY TO POSTOPERATIVE SEPSIS IN PATIENTS WITH IMPAIRED MONOCYTE IL-12 PRODUCTION

IL-12 is a potent immunoregulatory cytokine that is essential for the development of protective immunity, as demonstrated by numerous animal models of infection, Here, we provide evidence for a critical role of IL-12 in human sepsis, The results of a prospective study of 184 pati ents undergoing major elective surgery of the upper and lower gastroin testinal tract revealed that, in contrast to patients showing uneventf ul recovery, monocyte IL-12 production was severely and selectively im paired in patients developing postoperative sepsis, Moreover, the exte nt of monocyte IL-12 suppression correlated with the severity of posto perative: sepsis, Monocyte IL-12 secretion was suppressed before surge ry and remained low until the onset of sepsis, Therefore, the suppress ion of IL-12 secretion preceded the onset of postoperative sepsis but did not occur as a consequence of major surgery. In contrast, IL-1 bet a production was only reduced during the late postoperative course in patients developing postoperative sepsis, and TNF-alpha release was ev en increased at different time intervals before the onset of sepsis, T hus, reduced IL-12 release does not reflect a general defect in monocy te cytokine production. Consequently, these results establish a critic al role for IL-12 in early resistance to postoperative infection and m ay allow for the development of novel therapeutic strategies designed to stimulate host defense mechanisms and to reduce the incidence and s everity of septic complications.