Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A profound inflammatory response is initiated immediately following traumatic brain injury (TBI) and is characterized by the release of several cytokines with pro- and anti-inflammatory functions. In order to elucidate which cytokines are released in the human brain in response to injury as well as in the peripheral compartment, IL-1, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta were monitored in CSF and serum of severely brain-injured patients. Furthermore, we investigated the possible modulation of systemic reactions by IL-6 and the ability of IL-6 and IL-8 to promote the synthesis of nerve growth factor.
Mol Psychiatry 1997 Mar
PMID:Production of cytokines following brain injury: beneficial and deleterious for the damaged tissue. 910 36

Ribonuclease protection assay was used to demonstrate mRNA expression of several cytokines as well as inducible NO synthase (iNOS), constitutive endothelial NO synthase (cNOS) and perforin in the myocardium during the course of experimental autoimmune myocarditis (EAM) in rats. Interleukin 2 (IL-2) appeared in the initial inflammatory phase (day 14), subsided in the maximum inflammatory phase (day 19) and disappeared by the recovery phase (day 25). mRNA of IL-3 beta, interferon gamma INF-gamma and tumor necrosis factor alpha (TNF-alpha) were detected only in the maximum inflammatory phase and iNOS also appeared for several days at this time. In contrast. IL-10 mRNA was detected after the maximum inflammatory stage and persisted into the recovery phase (days 25-36). Although transforming growth factor beta 1 (TGF-beta 1) could be detected in all phases, the expression was markedly enhanced in the maximum inflammatory phase and gradually diminished (around day 36) to basal levels. Perforin mRNA was not detected at any point in the disease. Besides macrophages and CD4 T cells, a number of neutrophils were found in the myocardium especially at peak inflammatory stage. We suggest that antigen (Ag) primed Ag presenting cells or macrophages interact with T cells (Th1) to produce IL-2 and subsequent IFN-gamma, which further activates macrophages in the myocardium. Consequently, TNF-alpha and iNOS may inflict tissue damage to myocardium. It is also suggested that TGF-beta) and one representative Th2 cytokine, IL-10, help inhibit inflammation. These findings suggest that Th1 and Th2 cytokines are produced at different stages of EAM and modulate the inflammation and the course of EAM.
J Mol Cell Cardiol 1997 Feb
PMID:Characterization of cytokine and iNOS mRNA expression in situ during the course of experimental autoimmune myocarditis in rats. 914 Aug 9

Selective accumulation of eosinophils and activated CD4+ cells is now considered a central event in the pathogenesis of asthma, and this process is thought to be mediated by a number of cytokines including tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the Type 2 cytokines interleukin-4 (IL-4) and IL-5. To carry out a detailed time-course analysis of cellular changes in the bronchoalveolar lavage fluid (BAL), peripheral blood (PB), and bone marrow (BM), and of changes in the aforementioned cytokines in BAL and serum, Balb/c mice were sensitized by intraperitoneal injection with ovalbumin (OVA) adsorbed to aluminum hydroxide on two occasions 5 days apart, and were subjected to an OVA aerosol challenge 12 days after the second sensitization. This resulted in an airways inflammatory response characterized by early transient neutrophilia, marked eosinophilia, and, to a lesser extent, lymphocytosis in the BAL. Inflammatory events were first observed 3 h and 24 h after antigen challenge in the lung tissue and BAL, respectively, and lasted for 21 days. In the BM, we detected a 1.5- and 5-fold increase in the total number of cells and eosinophils, respectively, 4 days after the second sensitization. This was followed by a decrease, although BM eosinophilia remained clearly present at the time of antigen challenge. A second eosinopoietic event was observed in the BM shortly after challenge and reached a peak at day 3. BM cellularity returned to normal at day 21 after challenge. Serum OVA-specific IgE was first detected 3 days following the second sensitization (150 ng/ml). IgE levels then decreased but remained at the 75 ng/ml range at the time of the aerosol challenge. During the sensitization period, TNF-alpha (approximately 25 pg/ml), IL-4 (approximately 40 pg/ml), and IL-5 (approximately 250 pg/ml) were detected in serum, but not in the BAL fluid (BALF) and returned to background levels at the time of the antigen challenge. After antigen challenge, TNF-alpha, IL-4, IL-5, and GM-CSF were detected in serum. Peak levels were observed at 3 h (approximately 40 pg/ml), 3 h (approximately 120 pg/ml), 12 h (approximately 350 pg/ml), and 3 h (approximately 10 pg/ml), respectively, and returned to background levels 24 h after challenge. In the BALF, we detected peak levels of TNF-alpha, IL-4, IL-5, and GM-CSF at 6 h (approximately 250 pg/ml), 24 h (approximately 140 pg/ml), 24 h (350 pg/ml), and 3 h (approximately 10 pg/ml), respectively, with a return to background levels 5 days after challenge. No IL-10 could be detected at any time point during sensitization or after challenge in either serum or BAL. We also detected approximately 40 pg/ml of interferon-gamma (IFN-gamma) in the serum of normal untreated mice. Serum IFN-gamma levels fluctuated during sensitization and after challenge, but never exceeded those observed in untreated mice. Thus, the cytokine profile observed in this experimental model of allergic inflammation is characterized by IL-4 and IL-5 dominance, with an apparently minor TNF-alpha and GM-CSF contribution and relatively low or undetectable levels of IFN-gamma and IL-10.
Am J Respir Cell Mol Biol 1997 May
PMID:Cytokine and eosinophil responses in the lung, peripheral blood, and bone marrow compartments in a murine model of allergen-induced airways inflammation. 916 Aug 31

Plasma levels of antiinflammatory compounds (which counteract inflammation, cortisol, IL-1 receptor antagonist, IL-1ra; soluble IL-2 receptor, sIL-2r, soluble intercellular adhesion molecule-1, sICAM-1; interleukin-10, IL-10) were synchronously determined in a consecutive series of 25 patients with severe bacterial infections. Serum levels of cortisol, IL-1ra, sIL-2r, sICAM-1 and IL-10 were significantly higher in patients with infection compared with healthy volunteers. Bacterial infection results in the production of inflammatory and proinflammatory cytokines from macrophage/monocyte, which are thought to be involved in the pathogenesis of systemic inflammatory response syndrome (SIRS). We found that counter-inflammatory compounds can also be released during infectious insults. These results suggested that the biological activity of inflammatory mediators is inhibited by natural antiinflammatory compounds, and the body itself might down-regulate excessive inflammatory cascades through counteracting the inflammatory responses and restore homeostasis.
Res Commun Mol Pathol Pharmacol 1997 Apr
PMID:Clinical value of cytokine antagonists in infectious complications. 917 65

Intraovarian cytokines play a pivotal role in the normal growth and development of the ovarian follicle. The purpose of this study was to investigate the pattern of cytokine mRNA expression in ovarian endometriomata. A total of 10 patients with histologically confirmed endometriomata undergoing surgery formed the study group while nine patients undergoing sterilization with no evidence of a cyst in the ovary formed the control group. Biopsies of the ovary were obtained at surgery and stored in liquid nitrogen until processed by reverse transcription-polymerase chain reaction amplification to identify the presence of mRNA for interleukin (IL)-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). IL-6 and IL-10 mRNA were expressed by nine and seven patients respectively in the endometriosis group compared with three and one patients in the control group; this difference was significant (P < 0.05). IL-1 alpha mRNA was expressed by seven of 10 patients with endometriosis but by only one of the control group; this was again significantly different (P < 0.04). Ovarian IL-2 and IL-4 mRNA were not expressed in either group. There was no significant difference in the expression of IL-8, IL-13, IFN-gamma and TNF-alpha mRNA in the two groups. These findings suggest that abnormal local expression of certain cytokines may contribute to the development of endometriomata.
Mol Hum Reprod 1997 May
PMID:The pattern of cytokine mRNA expression in ovarian endometriomata. 923 23

Tumor necrosis factor alpha (TNF-alpha), a major product of alveolar macrophages (AM), has been implicated in many pulmonary diseases. Histamine, a mediator important in pulmonary inflammation, has been demonstrated to regulate the production of TNF-alpha by monocytes. In this study, we show that human AM and monocytes differ in their responses to histamine. Whereas histamine suppressed lipopolysaccharide (LPS)-stimulated TNF-alpha production by monocytes through a cAMP-dependent mechanism, it had no effect on either cAMP levels or TNF-alpha production by AM. In contrast, both PGE2 and IL-10 suppressed LPS-stimulated TNF-alpha production by AM and monocytes. The lack of response of AM to histamine appears unique, as histamine suppressed LPS-stimulated TNF-alpha production by mononuclear cells isolated from sites of acute and chronic inflammation, as well as from noninflammatory tissues, and by macrophages differentiated in vitro. In the presence of the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine, histamine increased cAMP levels in AM. Freshly isolated monocytes and AM did not differ in PDE activity. However, PDE activity in AM, but not in monocytes, was increased 15 min after culture with histamine and may, in part, be responsible for the inability of histamine to suppress TNF-alpha production by AM. However, this increase was small and we hypothesize that additional mechanisms may contribute to the unresponsiveness of AM to histamine. We suggest that the lack of response of AM to histamine may be important in the host defense function of AM in the distal lung.
Am J Respir Cell Mol Biol 1997 Aug
PMID:Inability of histamine to regulate TNF-alpha production by human alveolar macrophages. 927 10

Cachexia consists of a constellation of metabolic changes that occur in cancer patients, including the reduction of muscle and fat tissue, asthenia, anorexia, hypoglycemia and hypercalcemia. These syndromes complicate therapeutic intervention and decrease the quality of life of the patient. This review discusses the involvement of cytokines in cancer cachexia and describes the contribution of IL-6 and other cytokines to the wasting of C-26-bearing mice. The neutralization of IL-6 by antibody, or IL-6 receptor antagonism by suramin, significantly reduce the severity of key parameters of cachexia. The participation of several other factors (PGE2, IL-1, IL-10 and TNF-alpha) in the cellular communication between the C-26 tumor cell and tumor-infiltrating macrophages is also described.
Cytokines Mol Ther 1995 Jun
PMID:Inhibition of experimental cancer cachexia by anti-cytokine and anti-cytokine-receptor therapy. 938 67

Production of growth factors may provide a mechanism for disease evolution in some leukemias. Interleukin-1 is a plelotropic cytokine with the ability to synergize with other growth factors as well as to stimulate their production and release. Autocrine and/or paracrine secretion of interleukin-1 has been implicated in the pathogenesis of both chronic and acute myelogenous leukemia. Recently, a series of both specific and nonspecific IL-1 inhibitory molecules have been identified. These include IL-1 receptor antagonist, soluble IL-1 receptors, IL-1-converting enzyme inhibitor, IL-4, IL-10 and IL-1-antisense. Early experiments demonstrating the ability of some of these molecules to inhibit acute and chronic myelogenous leukemia growth suggest that clinical trials of these compounds may provide a novel management approach in these malignancies. Here we review the potential biologic and therapeutic role of IL-1 and its inhibitors in the myeloid leukemias.
Cytokines Mol Ther 1995 Sep
PMID:Interleukin-1 and its inhibitors: a biologic and therapeutic model for the role of growth regulatory factors in leukemias. 938 74

AK-5, a rat histiocytoma, grows as ascites and undergoes spontaneous regression upon subcutaneous transplantation. Earlier studies from this laboratory have demonstrated that immunogenic rejection of AK-5 tumor is mediated through ADCC involving CD8+ NK cells and anti-AK-5 antibody. Upon subcutaneous transplantation, 55-60% of animals initiated tumor regression between 12-15 days after tumor transplantation (early rejectors), while 40-45% did not evoke regression up to 20-25 days (late rejectors). In order to delineate this differential response among syngeneic animals to the same tumor, we have evaluated the cytokine profiles in circulation of both early and late rejecting animals. Our results show that an increase in IL-2, IFN-gamma, IL-4, IL-12 and TNF-alpha contributed to early regression, suggesting a predominantly Th-1 type of cytokine function being evoked against AK-5 tumor. Hosts with lower circulating levels of these cytokines showed delayed tumor regression. In addition, administration of anti-IL-4/anti-IL-4 + anti-IL-10 lead to a decreased antibody response to AK-5 surface antigens in vivo. Neutralization of IFN-gamma in tumor-bearing animals resulted in inhibition of NK-cell-mediated cytotoxicity against AK-5 cells and delayed the regression process. The present study suggests that early regression of AK-5 tumor depends primarily on the higher levels of circulating Th-1-type cytokines; however, the role of IL-4 and anti-AK-5 antibody in tumor regression cannot be ruled out.
Cytokines Mol Ther 1996 Mar
PMID:AK-5 tumor-induced modulation of host immune function: upregulation of Th-1-type cytokine response mediates early tumor regression. 938 88

Chronic hemodialysis (HD) patients have defects in cell-mediated immunity. To investigate the mechanisms underlying this immunodeficiency, we studied the production of cytokines in peripheral blood mononuclear cells (PBMC) from HD patients. PBMC from 22 HD patients and 20 healthy controls were cultured for 48 h in the presence or absence of phytohemagglutinin (PHA), lipopolysaccharide (LPS), or tuberculin purified protein derivative (PPD). Cytokine levels were measured by enzyme-linked immunosorbent assays. Only 64% of HD patients had a positive tuberculin skin test compared to 90% of normal Japanese controls. HD patients showed a diminished proliferative response to PHA. Compared to healthy controls, stimulated PBMC from HD patients produced similar amounts of T cell-derived cytokines (interleukin-2 (IL-2) and interferon-gamma (IFN-gamma)), but greater amounts of monocyte-derived inflammatory cytokines (IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), and IL-8) and a regulatory cytokine (IL-10). IL-10 production was positively correlated with IL-1 beta and TNF-alpha in healthy controls, whereas no correlation was observed in HD patients. Abnormal cytokine production by monocytes may contribute to the immunodeficiency seen in HD patients.
Res Commun Mol Pathol Pharmacol 1997 Oct
PMID:Increased production of interleukin-10 and inflammatory cytokines in blood monocytes of hemodialysis patients. 943 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>