Cytokine
The expression and biological role of 55- and 75-kDa tumour necrosis factor-receptors (TNF-RI and TNF-RII) in human polymorphonuclear cells (PMN) in vitro were studied using agonistic rabbit polyclonal anti-TNF-R antibodies. PMN express TNF-RII predominantly, and release the superoxide anion on stimulation by human recombinant lymphotoxin (LT) in vitro. Anti-TNF-RI but not anti-TNF-RII antibody stimulated...
Cytokines regulate the expression of specific sets of proteins which mediate their biological effects. We have comprehensively delineated the regulation of the human tryptophanyl-tRNA synthetase (hWRS) by eight different cytokines (including IFNs) and poly(I).poly(C) in several cell lines. Six non-lymphoid cell lines were tested, and all of these produced human, IFN inducible hWRS (γ2) mRNA upon stimulation...
TNF-α, IL-1, IL-6 and TGF-β are important macrophage-derived mediators which play the pleiotropic role in inflammatory, metabolic, hematopoietic and immunologic processes. Studies have shown that haemorrhagic shock without significant tissue trauma induces profound immunosupression which is associated with elevated plasma levels of TNF-α IL-1, IL-6 as well as TGF-β. Furthermore, Kupffer cells but...
IL-1 biology has taken on a new dimension with the discovery of the IL-1 receptor antagonist (IL-1ra). The balance in the production of monocyte-derived IL-1 and IL-1ra may impact on subsequent IL-1-dependent inflammation. Cancer patients are known to have impaired monocyte biological function. Interestingly, cancer patients receiving chemotherapeutic regiments containing cisplatinum appear to regain...
The involvement of cyclic nucleotides and of phosphodiesterase activities in IL-4-induced IgE production and release of the soluble form of the low affinity receptor for IgE (sCD23) by normal human peripheral blood mononuclear cells (PBMC) was evaluated. PBMC were stimulated by a suboptimal dose of IL-4 (10 ng/ml) cAMP inducers, adrenaline (ADR) and cholera toxin (CTx), which were found to potentiate...
Interleukin 10 (IL-10) is a pleiotropic growth and differentiation factor with potent suppressor functions on macrophages, T cells and NK cells and contributes to the regulation of proliferation and differentiation of B cells. The expression of IL-10 appears to be tightly regulated, as the levels of constitutive expression in normal cells is extremely low. In contrast to normal haematopoetic cells,...
The pleiotropic cytokine tumour necrosis factor-α (TNF) is thought to play a central role in infectious, inflammatory and autoimmune diseases. Critical to the understanding and management of TNF-associated pathology is the development of highly specific agents capable of modifying TNF activity. We evaluated the ability of a high affinity mouse/human chimeric anti-TNF monoclonal antibody (cA2) to neutralize...
Two soluble receptors of tumour necrosis factor were evaluated for development as potential therapeutic agents for inflammatory disease. The recombinant human soluble Type I and Type II TNF receptors, rsTNF-RI and rsTNF-RII, were expressed at high levels in E. coli, refolded, and chromatographically purified to homogeneity. The potencies of both recombinant soluble receptors were similar to their...
This study demonstrates that granulocytopenia alters the TNF response to endotoxin. Significantly higher levels of bioactive TNF were observed in mice rendered granulocytopenic (<0.05 x 10 9 granulocytes/litre) with cyclophosphamide than in normal mice. Levels of circulating soluble TNF receptor p75 (sTNFR-p75) in response to endotoxin were higher in normal mice than in granulocytopenic...
In this study we demonstrate that the cytokines IL-4 and IL-13, but not IL-10, can induce osteoblast chemotaxis. Recombinant IL-4 (rIL-4) and rIL-13 mediated cell migration was observed using a modified multi-well Boyden chamber system. Maximum chemotaxis was observed at concentrations of 100 ng/ml of both rIL-4 and rIL-13 with a chemotactic index of 2.0 +/- 0.1 and 2.3 +/- 0.4, respectively in this...
We investigated the biochemical properties of the 80 kDa binding subunit (gp80) of the human interleukin 6 receptor (IL-6R) in the genetic environment of the amphibian Xenopus laevis. In vitro transcribed mRNA encoding full length human gp80 was microinjected into Xenopus laevis stage VI oocytes. Protein expression was monitored by iodinated IL-6 and human gp80-specific monoclonal antibodies (mAb)...
Intracerebroventricular (ICV) injection of interleukin (IL)-1α has previously been demonstrated to enhance the rate of whole body glucose disposal. The purpose of the present study was to identify the specific tissue(s) responsible for the increased glucose uptake. All experiments were performed on fasted catheterized rats in which an ICV cannula had also been implanted. In vivo glucose uptake by...
When administered as single agents, both interferon gamma (IFN-γ) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the...
The presence of positive acute phase proteins within the circulation of rheumatoid arthritis patients suggests that elevated cytokine production associated with this chronic inflammatory disorder initiates the hepatic acute phase response. Cytokines produced at inflammatory lesions are believed to travel via the circulation to the liver where they induce acute phase protein production by hepatocytes...
To evaluate the value of serum interleukin 6 (sIL-6) for the prediction of therapeutic effect and adverse reaction after transcatheter arterial embolization (TAE), sIL-6 was measured before and after angiography or TAE in 18 patients (three after angiography and 15 after TAE for hepatocellular carcinoma). The three patients with only angiography showed no elevation of sIL-6, while a significant increase...
Pretreatment of LPS-induced RAW 264.7 cells with three PKC inhibitors suggests that induction of TNF-α, nitric oxide (NO), gelatinase B (Gel B) and IL-6 involves at least three distinct signalling pathways. We confirmed the PKC dependence of TNF-α and NO productions and found that Gel B was inhibited by Calphostin C (CAL), but potentiated by staurosporine (STAR) and CGP 41 251. IL-6 production was...
ICAM-1-mediated cell-cell adhesion is essential for different immunologic functions including non-MHC-restricted cytotoxicity. The shedding of a soluble form off ICAM-1 from melanoma impairs immune recognition and leads to tumour escape. Pretreatment of the Foss human melanoma cell line with HILDA/LIF or OSM, two cytokines involved in acute-phase response, increased the expression of membrane ICAM-1...
A cancer cell transfection model was used to evaluate biological activity of soluble IL-6 receptor (sIL-6R) in vivo. B-78 melanoma cells were stably transfected with cDNAs encoding human IL-6, murine sIL-6R and human leukaemia inhibitory factor (LIF). Control and transfected cells were intravenously (i.v.) and/or subcutaneously (s.c.) injected into B57BL/6 × C3H or SCID mice. Whereas B-78 cells formed...
Monocyte chemotactic proteins 2 and 3 (MCP-2 and MCP-3) are chemokines structurally and functionally related to MCP-1. In contrast to MCP-1, they are produced in low amounts by stimulated leukocytes or tumour cells. As an alternative method to generate sufficient protein for in vitro and in vivo characterization of MCP-2 and MCP-3, we have synthesized both 76-residue chemokines using Fmoc chemistry...