Regulation of the production of pro-inflammatory cytokines and antagonists during chemotherapy-induced neutropenia in patients with haematological malignancies.

Cytokine profiles were studied during 19 episodes of chemotherapy-induced neutropenia in 17 patients with haematological malignancies. Circulating concentrations of interleukin 1 alpha (IL-1 alpha), tumour necrosis factor alpha (TNF-alpha) and IL-1 receptor antagonist (IL-1ra) were measured before chemotherapy and thereafter three times weekly. During and after chemotherapy no significant changes were found in circulating cytokines. After start of chemotherapy, the ex-vivo LPS-stimulated production of cytokines in whole blood decreased and subsequently disappeared 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 circulating neutrophil or monocyte also decreased significantly, and was restored after completion of chemotherapy. These results show that the production of IL-1 beta, TNF-alpha and IL-1ra in blood disappears during chemotherapy-induced neutropenia, not only due to the decreased number of producing cells, but also as a result of a decreased production per cell, suggesting a mechanism of downregulation.