Dysregulated Cytokine Production by Monocytes from Chronic Lymphocytic Leukemia Patients

Abstract

The serum levels of proinflammatory cytokines (Tumor Necrosis Factor, Interleukin-1, Interleukin-6) in B-cell Chronic Lymphocytic Leukemia (CLL), and secretion of these cytokines by monocytes from CLL patients has been studied in 27 CLL patients and 20 normal subjects under unstimulated and stimulated conditions. It has been observed that monocyte function is impaired and deficient in CLL patients. The cytokine secretion though decreased in unstimulated cultures, was found to reach normal levels as far as IL-6 and TNF are concerned, indicating a possible role of an in vivo suppressive factor. The observed defect in cytokine production may have an important implication for the immune system of the patients.

Identification of outcome-correlated cytokine clusters in chronic lymphocytic leukemia

“…13 In our study, CCL3 and CCL4 were among the most effective in distinguishing CLL from healthy subjects ( Figure 1B) and also correlated with shorter TTFT (Figure 2E), as did IL-10 and IL-12. In contrast, we found IL-1␤ and IL-8, previously shown to associate with poor prognosis in CLL, [10][11][12] to correlate with good prognostic markers, increased survival, or both ( Figures 2-3); this discrepancy could reflect variable expression of these cytokines during the disease or their pleiotropism, exerting both pro-and antitumor actions in different contexts. 34 In addition, this apparent discrepancy indicates the downside of correlating the complexities of disease severity with levels of individual cytokines.…”

“…[10][11][12] Therefore, the positive correlation between CL2 and good outcome that we observe seems paradoxical. However, elevated levels of these 4 proinflammatory cytokines are characteristic features of Th1-skewed immune responses, which promote antitumor immunity.…”

“…[8][9][10][11][12][13][14]33 Of these cytokines, CCL3, CCL4, IL-1␤, IL-6, IL-8, IL-10, and IL-12 correlate with survival 10 or TTFT. 13 In our study, CCL3 and CCL4 were among the most effective in distinguishing CLL from healthy subjects ( Figure 1B) and also correlated with shorter TTFT (Figure 2E), as did IL-10 and IL-12.…”

“…7 Individual, specific cytokines and chemokines have been reported to be elevated in the sera, plasma, or both of CLL patients and to correlate with clinical course and outcome. [8][9][10][11][12][13][14] For example, high serum levels of IL-10, a cytokine that regulates inflammation, correlate with shorter survival. 10 In addition, plasma levels of CCL3 and CCL4, 2 inflammatory chemokines that regulate cell recruitment and activation, are elevated in CLL and correlate with time-to-first treatment (TTFT) 13 ; these chemokines are secreted by nurse-like cells and by CLL cells in response to B-cell receptor (BCR) engagement, 15 and their secretion by leukemic cells can be downregulated by small-molecule inhibitors of BCR signaling, 15,16 linking chemokines with another environmental influence on CLL-antigen stimulation.…”

Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines

“…2.5 pg/ml) and IL-10 (approx. 1 pg/ml) levels measured in normal subjects [34,35,36,37,38,39,40,41,42,43,44,45]. In patients with septic shock the lower level of expression of TNF-a resulted in a lower "basal" TNF-a/IL-10 ratio in monocytes and granulo-cytes.…”