Pathogenesis of fever of unknown origin in patients with acute leukemia and granulocytopenia.

Interleukin-1 (IL-1) is an endogenous pyrogen produced by blood monocytes or tissue macrophages in response to infection. Since hepatic macrophages (Kupffer cells) make up more than 90% of tissue macrophages and have a possibility of remaining intact after cytotoxic chemotherapy, they may be the major producers of IL-1 in infection during prolonged periods of severe monocytopenia in leukemic patients having modern chemotherapy treatment. Hence, the majority of febrile episodes probably due to infection in patients with acute leukemia and granulocytopenia may be caused by an inflammatory response mediated by IL-1 derived from the Kupffer cells in the liver sinuses.