Rise In Interleukin-6 Research Articles

Cytokine signaling during myocardial infarction: sequential appearance of IL-1 beta and IL-6.

The purpose of this study was to investigate the significance of the sequential changes in proinflammatory cytokines observed in the plasma of patients early after myocardial infarct: a rise in interleukin (IL)-1 beta (308 +/- 126 vs. 141 +/- 78 pg/ml, P < 0.01) between 0 and 2 h followed by an IL-6 peak (49 +/- 24 vs. 14.5 +/- 13 pg/ml, P < 0.01) 4-9 h later. No significant changes in tumor necrosis factor-alpha (TNF-alpha) were observed at this early stage. The linkage between IL-1 beta and IL-6 secretions is supported by 1) the ability of patient's plasma drawn early after myocardial infarction to induce IL-6 mRNA and protein synthesis in cells that may be potential targets in vivo (fibroblasts and endothelial cells), 2) suppression of this activity by antibodies against IL-1 beta, and 3) a delay between IL-1 beta and IL-6 peaks in vivo (4-9 h), which is similar to the time required for maximal IL-6 production in IL-1 beta stimulated target cells in vitro (6 h). This sequential signaling might serve as the basis for an amplification mechanism of proinflammatory cytokines. In fact, a much greater synthesis of C-reactive protein was observed in hepatocytes when stimulated with conditioned medium of fibroblasts or endothelial cells that had previously been incubated with plasma of patients. The results of our work strongly suggest that, by inducing IL-6 in potential target cells, IL-1 beta could act as the primary, but indirect, signal that stimulates acute-phase protein synthesis after myocardial injury.

Adoptive Immunotherapy with Autologous Macrophages: Current Status and Future Perspectives

Adoptive immunotherapy is a treatment modality designed to correct a defective and/or insufficient host defense response to a malignant tumor. Recently, we have developed a large scale technology for the generation of tumor cytotoxic macrophages (MACs) from circulating precursor monocytes. These ex vivo matured and interferon-gamma-activated MACs were used for adoptive transfer in a total of 30 tumor patients by intravenous (n = 12), intraperitoneal (n = 11) and intrahepatic (n = 7) infusion. A biological response to autologous cell transfer was evident from low-grade fever, elevation of C-reactive protein, induction of the coagulation cascade and a rise in interleukin-6 in sera as well as in ascitic fluids. A clinical response was only seen upon intraperitoneal treatment and consisted of palliation of malignant ascites in 3 of 7 patients and in reduction of ascitic tumor markers (CEA, CA125). Future perspectives of MAC therapy in combination with macrophage colony-stimulating factor, bacterial endotoxins and synthetic derivatives as well as monoclonal antibodies against tumor-associated antigens are discussed. Furthermore, the ex vivo manipulation of the MAC system may offer the possibility to use these multifunctional, pleiotropic effector cells not only in malignancy but also for the therapy of complicated opportunistic infections and secondary bone marrow hypoplasia.

In vivo evidence that the rise in plasma IL 6 following injection of a fever-inducing dose of LPS is mediated by IL 1β

Although it has often been speculated that Interleukin (IL) 1 alpha and IL 1 beta are circulating endogenous pyrogens (EP), there are few data demonstrating an elevation of these cytokines in the plasma of febrile animals. We hypothesized that IL 1 is released locally and may act to stimulate the release of another pyrogen, IL 6, which circulates to the brain to cause fever. The major purpose of the present study was to determine whether pretreatment of rats with antiserum to IL 1 beta, which attenuates lipopolysaccharide (LPS) induced fever, also results in an attenuation of the rise in plasma and cerebrospinal fluid (CSF) concentrations of IL 6. Our results show that injection of IL 1 beta produced dose-dependent rises in temperature and increases in plasma and CSF IL 6 activity, and that pretreatment of rats i.v. with antiserum to IL 1 beta produced a 55% decrease in the fever caused by LPS injection, a 68% decrease in plasma IL 6, and a 67% decrease in CSF IL 6. These data confirm the findings of previous studies that IL 1 beta is required for a portion of LPS-induced fever and also provide the first in vivo demonstration that the rise of IL 6 in rats injected with a fever-inducing dose of LPS can be significantly blocked by antiserum to IL 1 beta. Overall, the data in our study can be interpreted as being consistent with the hypothesis that the pyrogenic effect of IL 1 beta is mediated mainly through the release of IL 6, but conclusive confirmation of this hypothesis must await studies with antibodies to IL 6.