Induction of interleukin-1 receptor antagonist (IL-1ra) following surgery is associated with major trauma.

Injury and trauma are major inducers of the acute-phase response. Among the major cytokine mediators of this response is interleukin-6, which is considered to be an early indicator of tissue damage following trauma. We have previously reported, in a group of children undergoing a single abdominal surgical procedure, the early induction of interleukin-1 receptor antagonist following the commencement of surgery. In the present study, we investigated the production of cytokines IL-1ra, IL-1β, and IL-6 in patients undergoing a range of surgical procedures to examine whether IL-1ra release is a general phenomenon or is restricted to certain categories of surgery. Peripheral blood mononuclear cells and polymorphonuclear leukocytes from patients were studied as a possible source of induced IL-1ra. IL-1ra and IL-6 were induced in 44 and 53 of the 73 patients, respectively. Induction of these cytokines was associated with major operative procedures of the abdomen and thorax and in hip replacement. Levels of these two cytokines varied widely within the different surgical categories. IL-1ra reached maximum levels before IL-6 in 18 patients and at the same time in 20 patients. IL-1β levels were induced in only 6 patients. Endotoxin levels were not detected in association with induction of IL-1ra. IL1-ra was not upregulated in peripheral blood mononuclear cells or polymorphonuclear leukocytes obtained from patients following surgery suggesting that these cells are not the source of plasma IL-1ra induced following trauma. These results provide new insights into the regulation of IL-1ra in vivo in humans. They show that IL-1ra can be induced as an early-response cytokine following major trauma in the absence of an infectious etiology.