Regulated plasma levels of colony‐stimulating factors, interleukin‐6 and interleukin‐10 in patients with acute leukaemia and non‐Hodgkin's lymphoma undergoing cytoreductive chemotherapy

Abstract

Endogenous plasma levels of granulocyte colony stimulating factor (G- CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF),IL-6 and IL-10 were measured in a total of 70 patients undergoing cytoreductive chemotherapy for treatment of acute leukaemia or non-Hodgkin's lymphomas. the diagnoses were acute myeloid leukaemia (AML; n = 30), acute lymphoblastic leukaemia (ALL;n=6), non-Hodgkin's lymphomas (NHL; n=11) and other malignant haematological disorders including myelodysplastic syndromes (n=23). After chemotherapy, plasma G-CSF was elevated (mean 5.6 ng/ml; range 1.2-10 ng/ml), and was inversely correlated with white blood cell counts (WBC) (r=-0.7, p<0.001). Occurrence of fever (T>38.0 degrees C) during severe myelosuppression (WBC<1x10(9)/1) was associated with an additional increase of G-CSF levels (P<0. (P<0.001). Plasma IL-6 correlated significantly with fever (range <1 to 1100 pg/ml, mean 130 pg/ml; r=0.5, P<0.001) but revealed only a weak association with WBC or platelet counts. In patients treated with recombinant G-CSF (n = 9), an association between IL-6 and fever was still observed after chemotherapy. During the nonfebrile status (total n = 242; AML n = 124), IL-6 levels remained <9 pg/ml in 90% of cases, whereas G-CSF increased with leucopenia (r = -0.72;P<0.001). In contrast, endogenous GM-CSF remained normal and IL-10 showed only a slight increase (21% of samples; maximum 22 pg/ml) in severe leucopenia. In particular, IL-10 levels did not correlate with G-CSF or IL-6 levels. We conclude that systemic release of G-CSF and IL-6 is obviously nit abrogated by cytoreductive chemotherapy in acute leukaemia and NHL may add to the therapeutic efficacy of recombinant cytokines. Also, plasma levels of G-, GM-CSF or IL-6 appear to be regulated by separate mechanisms.

Additive effects of infection and neutropenia on the induction of granulocytopoietic activity in vivo

“…Considering IL-10 a likely candidate, researchers have previously looked at a possible correlation between IL-10 and G-CSF levels in adults, albeit disregarding a possible effect of infection. 11 Similar to their findings, no such correlation could be demonstrated here, not even after controlling for severity of infection. This is not entirely surprising because, despite the negative effect of IL-10 on monocytic G-CSF synthesis, Knopf et al 28 have demonstrated the failure of IL-10 to suppress G-CSF production from mature macrophages, presumably one of the two major sources of the G-CSF detected in the plasma of aplastic patients.…”

Elevated serum concentrations of hepatocyte growth factor in acute myelocytic leukaemia

“…Clearly, the natural sources of HGF in the circulation or HGF elimination pathways are affected by chemotherapy, and the data argue against a role for HGF in the recovery from neutropenia. The pattern of HGF levels is in marked contrast to G-CSF levels during neutropenic episodes (44,45). Furthermore, modest increases in IL-10 and TNF-a, but low IL-8 and GM-CSF levels have been found in neutropenia (18,45,46).…”

Oxaliplatin-Induced Fever and Release of IL-6

“…IL-6 is a proinflammatory cytokine with a broad spectrum of inflammatory and immunological activities, such as modulation of acute phase proteins, fever and stimulation of B lymphocytes [15]. In previous studies, it was shown to significantly correlate with body temperature in febrile episodes, but only a weak association with WBC or platelet counts [16]was found. The concentration of IL-6 was measured in serum or plasma during cytotoxic chemotherapy and fever of unknown origin, and was described as a valuable tool for the detection of sepsis in patients with hematological malignancies undergoing cytotoxic medication [17].…”