PresentationCytokine deregulation in cancer
Section snippets
IL-6 in relapsed hodgkin’s and non-Hodgkin’s lymphomas
During the 1980s, it was noted that patients who were treated with recombinant interferon (IFN)-gamma developed fever and night sweats reminiscent of B symptoms 19, 20. However, when levels of IFN-gamma were measured in the serum of lymphoma patients, no elevations were found 〚15〛. Furthermore, phytohemagglutinin-stimulated T lymphocytes from these individuals were actually deficient in IFN-γ production. These preliminary results suggested that IFN-γ was an unlikely cause of B symptoms.
IL-6 in diffuse large cell lymphoma
Diffuse large cell lymphoma (DLCL) is an aggressive lymphoma. About 50% of patients are curable. Patients who relapse after induction generally do so within 2 to 3 years and most of these patients succumb to their disease. Prognostic factors are critical to identifying the patients likely to relapse and designing better therapeutic regimens for them.
Serum IL-6 levels in DLCL patients were found to be significantly higher than those in normal volunteers (N = 33; median, undetectable; range,
Evidence for a pathogenic role for IL-6 in lymphomas
To date, prognostic variables for lymphomas (as well as for the majority of other cancers) have been clinical features that do not participate in the development of the disease process. They therefore represent surrogate markers for underlying biological variables. In contrast, there are several lines of evidence that support a pathogenic role for IL-6 in lymphoma. First, overexpression of IL-6 in transgenic mice is associated with the development of lymphomas 28, 29. Second, high IL-6 levels
Interleukin-10
Interleukin-10 (IL-10) is a pleiotropic cytokine produced by type 2 helper cells (Th2), as well as by monocytes and macrophages, and normal and neoplastic B lymphocytes. It is highly homologous to an open reading frame of Epstein-Barr virus (EBV) called BCRFI, and EBV infection of B-cells upregulates IL-10. IL-10 production has strong immunosuppressive effects via inhibition of TH1 type cytokines, including interferon gamma and interleukin-2 (table II). On B-cells, IL-10 has a potent
Homeostasis
A balance between cytokine agonists and antagonists is required for normal homeostasis. Several studies suggest that this balance is disrupted in some tumors. For instance, acute myelogenous leukemia cells show high levels of IL-1 beta and low levels of IL-1RA. (IL-1RA suppresses IL-1 activity by binding to the IL-1 receptor without agonist activity.) IL-1 beta acts as an autocrine growth factor for this leukemia as well as for chronic myelogenous leukemia. In patients with advanced chronic
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