Steep elevation of blood interleukin-6 (IL-6) associated only with late stages of cachexia in cancer patients.

Changes in blood cytokines of 28, consenting, terminally ill cancer patients were studied to determine a relationship between cachexia and changes in cytokine levels. Levels of PTHrP and five types of cytokines considered to be associated with cachexia, TNFalpha, IL-1beta, IL-6, IFNgamma and LIF, were measured during routine blood examination and were compared with clinical findings. With the exception of TNF-alpha, which was detected in one patient, only IL-6 was detected in all 28 patients recruited in this study. Ten patients showed a sharp elevation of IL-6 just before death, following a 40-day period in which IL-6 was continually detected in the blood. In six out of these ten patients, levels of 100 pg/mL or more of IL-6 were detected in the week prior to death. The average period between detection of these levels of IL-6 and death was 2.0 days. Progression of carcinoma is believed to induce a variety of cytokines, which cause loss of appetite, weight loss, tissue wasting, and finally patients may become cachectic. Of the six cytokines studied during this test, only the level of IL-6 was significantly elevated, and this sharp rise occurred approximately one week before patients died. We conclude that IL-6 increases only gradually during the early stages of cachexia but then shows a sudden and steep rise just before death.