REGULATION OF THE PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND ANTAGONISTS DURING CHEMOTHERAPY-INDUCED NEUTROPENIA IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

Cytokine profiles were studied during 19 episodes of chemotherapy-indu ced neutropenia in 17 patients with haematological malignancies. Circu lating concentrations of interleukin 1 alpha (IL-1 alpha), tumour necr osis factor alpha (TNF-alpha) and IL-1 receptor antagonist (IL-1ra) we re measured before chemotherapy and thereafter three times weekly, Dur ing and after chemotherapy no significant changes were found in circul ating cytokines. After start of chemotherapy, the ex-vivo LPS-stimulat ed production of cytokines in whole blood decreased and subsequently d isappeared completely in all patients, and recovered after the end of treatment. The decrease of cytokine production could not be attributed to the decreased number of cells only, as the net production per circ ulating neutrophil or monocyte also decreased significantly, and was r estored after completion of chemotherapy. These results show that the production of IL-1 beta, TNF-alpha and IL-1ra in blood disappears duri ng chemotherapy-induced neutropenia, not only due to the decreased num ber of producing cells, but also as a result of a decreased production per cell, suggesting a mechanism of downregulation. (C) 1997 Academic Press Limited.