Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00082 (IL-2)
 29,198 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) is a well-described and characterized cytokine which can be elicited in the intact animal by endotoxin. This factor produces necrosis of subcutaneous tumors in the classic model: Meth A sarcoma in the Balb C mouse. It has been shown to be cytostatic or cytotoxic for a variety of human cancer cell lines, as well as to have effects against both mouse tumors and human cancers carried in the nude mouse. TNF is most likely produced by the macrophage. TNF has been cloned, and has been shown to have a molecular weight of 17,000 and to contain approximately 157 acids in its active form. The genes responsible for TNF are contained on chromosome 6 in man, which also contains genes of the major histocompatibility complex. Although there are similarities to lymphotoxin, which is produced by mitogen-stimulated lymphocytes, and to interleukin-1 (IL-1), which is also produced by macrophages, TNF has distinctive differences, primarily in its antiproliferative effects. TNF is also allied with the effects of cachexia and has been shown to be similar to, if not exactly the same as, cachectin. Although it appears that effects of TNF require expression of receptors to facilitate binding to the cell, there is not a quantitative relationship between receptors and the sensitivity. TNF cytotoxic effects appeared to be amplified by pretreatment of cells with chemotherapeutic agents such as Actinomycin D, Adriamycin, and Cytoxan as well as to have synergistic effects with gamma interferon, alpha interferon, and IL-2. Although initial phase I and phase II studies of TNF in man have shown the expected toxicity, there have been minimal antitumor effects. It is anticipated that with more sophisticated studies, perhaps combining TNF with either biological or chemotherapeutic agents, TNF's true role in cancer therapy may well unfold.
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PMID:Tumor necrosis factors. 268 30

Recent studies have shown the existence of reciprocal links between cytokine activity and immunomodulating neurohormones or neuropeptides. In particular, the pineal hormone melatonin (MLT) appears to influence IL-2 activity in cancer. The present study was performed to evaluate which interaction exists between MLT and another important cytokine, tumor necrosis factor-alpha (TNF), which is responsible for both antitumor cytolytic activity and cancer-related cachexia. In a first study, we analyzed MLT circadian rhythm under TNF administration (0.75 mg/day i.v. for 5 days) in 10 metastatic solid tumor patients. In a second study, we evaluated TNF serum levels in 10 metastatic solid tumor patients under therapy with MLT alone (20 mg/day orally in the evening for at least 1 month). In a third study, we have measured concomitantly daily serum levels of MLT and TNF in 30 patients with metastatic solid neoplasms. Nocturnal mean serum concentrations significantly increased in response to TNF injection. MLT therapy induced a significant decline in TNF mean values. Finally, patients with abnormally high MLT diurnal levels showed significantly lower TNF mean concentrations with respect to those with normal levels of the pineal hormone. This study, by showing the stimulatory effect of TNF on MLT secretion and the inhibitory action of MLT on TNF release, would suggest the existence of feed-back mechanisms operating between the pineal gland and TNF released from macrophages in human neoplasms.
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PMID:Role of the pineal gland in the control of macrophage functions and its possible implication in cancer: a study of interactions between tumor necrosis factor-alpha and the pineal hormone melatonin. 766 Aug 55

Human immunodeficiency virus infection leads to a deregulated production of a number of cytokines. Some of them (IL-1, IL-6, TNF-alpha, interferon-gamma) are produced in increased amounts in vivo, whereas the production of IL-2 is decreased. This latter abnormality plays a pivotal role in the establishment of the immunodeficiency. Some cytokines (IL-1, IL-6, TNF-alpha) stimulate the in vitro replication of HIV, whereas others (mainly the interferons) inhibit it. The effect of cytokines in vivo in the spreading of HIV remains, however, largely unknown. Cytokines may also be involved in the development of many clinical manifestations associated with HIV infection. IL-1, IL-6 and TNF-alpha may play a role in tissue damages associated with opportunistic infections, in HIV-related encephalopathy and in cachexia. Cytokines, mainly IL-6, IL-10 and IL-13, may stimulate the growth of malignant cells during Kaposi sarcoma or lymphomas. Better knowledge of the role of cytokines during HIV infection should allow new therapeutic approaches based on the use of either recombinant cytokines or specific antagonists, with the aim of limiting both HIV spreading and the clinical manifestations of this infection.
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PMID:Cytokines in HIV infection. 792 84

The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.
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PMID:Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii. 917 93

Medroxyprogesterone acetate (MPA) is widely used in oncology both in the treatment of hormone-related cancers and as supportive therapy in anorexia/cachexia syndrome (ACS), but conclusive data are not yet available to explain its anticachectic effect. ACS is characterised by weight loss, changes in metabolism, reduction of appetite, nausea and vomiting. Several cytokines, mainly interleukin (IL)-1, IL-2, IL-6 and tumour necrosis factor alpha (TNF alpha), are involved in the pathogenesis of ACS. Additionally, nausea and vomiting can be mediated by factors inducing serotonin (5-HT) production and/or release by pleiotropic cells including activated T lymphocytes. In the present study, we report the effect of MPA on peripheral blood mononuclear cells (PBMC) from 10 cancer patients in advanced stage of disease (6 head and neck, 2 colon, 1 lung and 1 ovary). The proliferative response of PBMC to PHA, anti-CD3 monoclonal antibody (MAb) or recombinant IL-2 (rIL-2), the production of IL-1 beta, IL-2, IL-6, TNF alpha and 5-HT by PHA-stimulated PBMC and the expression of lymphocyte membrane-bound IL-2 receptor (IL-2R) subunities (CD25 and CD122) were studied. The addition of MPA significantly reduced the PBMC proliferative response to PHA and anti-CD3 MAb but not to rIL-2. MPA 0.2 microgram/ml was also capable of reducing the levels of IL-1 beta, IL-6, TNF alpha and 5-HT produced in culture by PHA-stimulated PBMC, whereas it did not induce any change in the percentage of PBMC expressing either CD25 or CD122 or both molecules after stimulation with PHA or anti-CD3 mAb.
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PMID:Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis by peripheral blood mononuclear cells of cancer patients. 927 42

Cytokines are hormonE-like proteins and peptides involved in the signalling between cells during immune response. They are produced mainly by lymphocytes (lymphokines) and mononuclear phagocytes (monokines). They are involved in both cell-mediated and humoral immunity. Cytokines fall into a number of categories: interferons (IFNs), interleukins (ILs) and growth factors. It has been indicated in cancer immunology the following cytokines are particularly important: IFNs, TNF-alpha, IL-1, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12. Interferons (IFN-gamma in particular) in cooperation with TNF-alpha and IL-1 inhibit proliferation of tumor cells and by their synergic activity with IL-2 induce cytotoxicity of NK-cells. They activate mononuclear phagocytes and by B lymphocyte stimulation augment lysis of cancer cells. TNF-alpha has mainly cytotoxic activity, leading to hemorrhagic necrosis of tumors. It is also an endogenic pyrogen which is together with IL-1 responsible for pyretic status in neoplastic disease. IL-1 stimulates necrotizing activity of TNF-alpha and augments cachexia by anabolism of lipid induction. IL-2, IL-6 and IL-12 induce NK and LAK-cell cytotoxicity. IL-12 inhibits metastasis formation. IL-10, by inhibiting synthesis of cytokines may lead to tumor development.
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PMID:Cytokines in lung cancer. 933 19

The in vitro responsiveness of peripheral blood mononuclear cells (PBMC) T lymphocytes was studied in 81 patients with limited or extended head and neck squamous cell carcinoma (HNSCC), as judged by T, N and T + N stages. Patients included in the study were males below 80 years of age, without auto-immune disease or cachexia, who were not taking any immuno-active medication at the time of diagnosis. The patients were divided into groups according to TNM stage T0-2 vs T3-4, N0-1 vs N2-3 or T + N0-3 vs T + N4-7. When cells from patients with early and late stage, according to T, N or T + N stage, were compared, we found a decreased level of mitogen stimulated T-cells and decreased spontaneous proliferation with increasing disease stage. The same was true if the in vitro mitogenesis of T-cells was analysed separately, depending on the laryngeal or oral cavity/pharyngeal origin of the patients' tumours. If the patients were divided into two groups based on N stage, decreased gamma-interferon, and to some extent interleukin (IL-2), but not IL-4 levels, were found to be related to the disease stage.
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PMID:Disease stage related in vitro responsiveness of peripheral blood T-lymphocytes in patients with head and neck carcinoma. 987 Jun 39

Raised serum levels of interleukin 6 (IL-6) have been described in cancer patients. This cytokine mediates the acute phase response and has been also involved in the pathogenesis of cancer cachexia. The objectives of the present study were: (1) to determine the relationships of IL-6 and other cytokines with neoplasia extension, acute phase response and nutritional status, in lung cancer patients; and (2) to establish the prognostic value of serum cytokine levels. A prospective study in which IL-1, IL-2, IL-6, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been determined in 66 newly diagnosed lung cancer patients. Nutritional status was assessed objectively. Serum levels of growth hormone (GH), insulin growth factor 1 (IGF-1) and acute phase reactants as C Reactive Protein, alpha1 antitrypsin and ferritine, were determined. Increased IL-6 levels were related to extensive disease, impaired performance status, enhanced acute phase response and malnutrition. Raised serum IL-6 levels, extensive disease, low Karnofsky index, malnutrition, acute phase response and low IFN-gamma were all related to a shorter survival. When assessed by a multivariate analysis, IL-6 kept its independent prognostic value together with age, disease extension, and decreased IFN-gamma serum levels.IL-6 is increased in lung cancer patients, enhances the acute phase response in them, and is correlated with poor nutritional status, impaired performance status and shorter survival.
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PMID:Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer. 1008 Aug 83

We have previously shown an increased T lymphocyte and monocyte responsiveness in peripheral blood mononuclear cells (PBMC) from patients with head and neck squamous cell carcinoma (HNSCC) compared with PBMC from control patients. This study reports T lymphocyte function of PBMC of 81 patients with HNSCC dependent on disease stage and prognosis. Males with HNSCC under 80 years of age without cachexia, with no auto-immune disease or previous cancer and on no immuno-active medication were included at the time of diagnosis of disease. The follow-up was for at least 18 months. When cells from patients with early vs late stage disease according to the T, N or T + N stage of HNSCC were compared, decreased in vitro mitogen-stimulated and spontaneous T cell proliferation was seen with increasing tumour stage. When patients were studied according to disease-specific survival, a decreased T lymphocyte mitogen-stimulated proliferation was observed to be associated with a poorer prognosis. No changes in prognosis were noticed related to decreased gamma-IFN, IL-2 or IL-4 level of the supernatants of the T lymphocyte-stimulated PBMC in vitro cultures. With stratification for disease stage, we determined that PBMC in vitro T lymphocyte-stimulated proliferation predicted outcome for the HNSCC patients. The results were similar for both laryngeal and oral cavity/pharyngeal cancers. The present investigation provides evidence to support the idea that the relationship between HNSCC and the immune system of the host may provide clinically useful information about prognosis.
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PMID:Peripheral blood mononuclear cell (PBMC) responsiveness in patients with head and neck cancer in relation to tumour stage and prognosis. 1032 92

Active human visceral leishmaniasis (VL) is characterized by a progressive increase in visceral parasite burden, cachexia, massive splenomegaly, and hypergammaglobulinemia. In contrast, mice infected with Leishmania donovani, the most commonly studied model of VL, do not develop overt, progressive disease. Furthermore, mice control Leishmania infection through the generation of NO, an effector mechanism that does not have a clear role in human macrophage antimicrobial function. Remarkably, infection of the Syrian hamster (Mesocricetus auratus) with L. donovani reproduced the clinicopathological features of human VL, and investigation into the mechanisms of disease in the hamster revealed striking differences from the murine model. Uncontrolled parasite replication in the hamster liver, spleen, and bone marrow occurred despite a strong Th1-like cytokine (IL-2, IFN-gamma, and TNF/lymphotoxin) response in these organs, suggesting impairment of macrophage effector function. Indeed, throughout the course of infection, inducible NO synthase (iNOS, NOS2) mRNA or enzyme activity in liver or spleen tissue was not detected. In contrast, NOS2 mRNA and enzyme activity was readily detected in the spleens of infected mice. The impaired hamster NOS2 expression could not be explained by an absence of the NOS2 gene, overproduction of IL-4, defective TNF/lymphotoxin production (a potent second signal for NOS2 induction), or early dominant production of the deactivating cytokines IL-10 and TGF-beta. Thus, although a Th1-like cytokine response was prominent, the major antileishmanial effector mechanism that is responsible for control of infection in mice was absent throughout the course of progressive VL in the hamster.
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PMID:The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response. 1116 Feb 39


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