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

We measured the plasma levels of anti-inflammatory cytokines, including interleukin 1 receptor antagonist (IL-1ra), IL-4 and IL-10; inflammatory cytokines, including IL-2, IL-6, IL-8 and tumor necrosis factor receptor I and II (TNFR I and TNFR II); and endotoxin in 11 patients with septic shock associated with gram-negative bacteria and 12 patients with sepsis not associated with shock. The plasma levels of IL-1ra and IL-10 were elevated in the septic shock group compared with the sepsis group. TNFR I and TNFR II levels tend to be higher in the septic shock group. The plasma level of TRNF-alpha was significantly correlated with levels of IL-1ra, IL-4, IL-10, TNFR I, and TNFR II. The elevated levels of the anti-inflammatory cytokines, TNFR I, and TNFR II, appeared to reflect an attempt to suppress the shock syndrome.
Res Commun Mol Pathol Pharmacol 1997 Oct
PMID:Anti-inflammatory cytokine levels in patients with septic shock. 943 13

Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts and activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regulation. TNF-alpha stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN-gamma alone had no effect. Both cytokines together did not induce greater IL-8 release compared to TNF-alpha alone. IL-1beta was more potent in inducing IL-8 release and, together with TNF-alpha, there was a synergistic augmentation of IL-8 release. IL-8 release induced by TNF-alpha and IFN-gamma was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13, as well as by dexamethasone. In addition to its contractile responses, airway smooth muscle cells have synthetic and secretory potential with the release of IL-8 and subsequent recruitment and activation of neutrophils in the airways. Release of IL-8 can be modulated by Th-2-derived cytokines and corticosteroids.
Am J Respir Cell Mol Biol 1998 Jan
PMID:Expression and release of interleukin-8 by human airway smooth muscle cells: inhibition by Th-2 cytokines and corticosteroids. 944 49

Idiopathic dilated cardiomyopathy (DCM) is characterised by a severe dysfunction of the heart muscle resulting in terminal heart failure. Its pathogenesis is believed to be multifactorial involving genetic predisposition, viral infection and autoimmunity, but little is known in detail, and there is no curative treatment except transplantation. Interleukin-1 (IL-1) mediates inflammatory responses to infection and injury. It can be produced by several widely-distributed cell types, including macrophages, and is thought to depress myocyte contractility by stimulating nitric oxide synthase. To investigate whether this pro-inflammatory cytokine may be a pathogenic mediator in DCM, IL-1beta mRNA and protein were evaluated in coronary arteries and myocardium from patients undergoing cardiac transplantation for DCM.IL-1beta mRNA was detected by PCR of cDNA and northern blots of mRNA in coronary arteries and myocardium from patients with DCM. By comparison, samples from patients with ischaemic heart disease (IHD) contained much less IL-1beta mRNA. In contrast, mRNA for other cytokines (TNFalpha, IL-6, IL-10, PDGFA) were similar in both pathologies. In DCM, IL-1beta mRNA and protein were localised to infiltrating macrophages in interstitial regions between myocytes, some of the myocytes themselves, and endothelial cells of vessels in the wall of the arteries. These results suggest that local production of the pro-inflammatory cytokine, IL-1beta may play a part in the pathogenesis of DCM.
J Mol Cell Cardiol 1998 Feb
PMID:Interleukin-1 in myocardium and coronary arteries of patients with dilated cardiomyopathy. 951 98

The study of experimental infection of inbred strains of mice with the intracellular protozoan parasite Leishmania major has contributed significantly not only to our understanding of this fascinating host/parasite relationship but also to that of many basic immunological phenomena. Much has been learned about the cognate interaction of antigen-specific T cells and antigen-presenting cells, about cytokine and T cell subset regulation, and the requirements for costimulation. Specifically, the immune response to experimental L. major infection is the paradigm for polarized T helper cell (Th) 1 and Th2 differentiation. In this model system a Th1 response characterized by interleukin (IL)-2 and interferon (IFN)-gamma secretion leads to self-curing disease, whereas a Th2 response (IL-4, IL-10) leads to nonhealing disease. Numerous manipulations, including the injection of cytokines and of neutralizing anti-cytokine antibodies, cytokine transgene expression, and more recently cytokine and cytokine receptor gene knockout studies, have all provided intriguing new pieces to the still incomplete mosaic of our understanding of the immune response. Some of these findings were clearly unexpected and are still incompletely understood. For instance, based on earlier neutralizing anti-IL-4 monoclonal antibody injection studies, IL-4 gene-disrupted BALB/c mice were expected to be unable to mount the biased Th2 response typical of the IL-4+/+ wild-type mice and to be able to control their lesions; quite unexpectedly, the BALB/c IL-4 knockout mice remain unable to heal their L. major infection. Based on these unexpected findings, we reexamine the literature in an attempt to resolve this apparent paradox and to relate the large body of experimental findings in the mouse system to that which is known about natural and experimental infections in the human.
J Mol Med (Berl) 1998 May
PMID:Progressive disease or protective immunity to Leishmania major infection: the result of a network of stimulatory and inhibitory interactions. 962 95

The effects of a Th1-cell-associated cytokine (interferon-gamma [IFN-gamma]) and Th2-cell-associated cytokines (interleukin [IL]-4, IL-10, and IL-13) on prostaglandin (PG) production by human alveolar macrophages (AM) were examined in terms of four parameters: PGE2 synthesis, cyclooxygenase (COX) activity, and the protein and mRNA of two COX isozymes (COX-1 and COX-2). Lipopolysaccharide (LPS)-stimulated PGE2 synthesis and COX activity were suppressed significantly by IL-4, but were not affected significantly by IL-10, IL-13, or IFN-gamma. The LPS-dependent increase in COX activity in AM was attributable to COX-2 because it was inhibited by NS-398 (a COX-2-specific inhibitor). Western and Northern blot analyses revealed that the LPS-induced increases in COX-2 protein and mRNA were attenuated by IL-4 but hardly affected by IL-10, IL-13 or IFN-gamma. In contrast, COX-1 protein and mRNA were hardly detected in any of the AM preparations. In AM and monocytes from the same individuals, LPS induced the synthesis of large amounts of PGE2 and COX-2 mRNA in AM, and of lesser amounts in monocytes. IL-4, IL-10, and IL-13 significantly suppressed LPS-dependent PGE2 synthesis and COX-2 mRNA induction in monocytes, whereas only IL-4 significantly suppressed them in AM. Furthermore, 15-lipoxygenase mRNA was detectable only in monocytes incubated with LPS plus IL-4. These results suggest that IL-4 is a potent regulator of PG production in AM, and that regulation of the arachidonic-acid (AA) metabolic pathway in cells of monocyte-macrophage lineage by Th2-cell-associated cytokines depends on the stage of cell differentiation.
Am J Respir Cell Mol Biol 1998 Aug
PMID:Comparison of the regulations by Th2-type cytokines of the arachidonic-acid metabolic pathway in human alveolar macrophages and monocytes. 969 3

The factors influencing the pathogenesis of autoimmune disease are not fully known, but the host genotype undoubtedly plays a role in determining the outcome of these diseases. The role of the host's major histocompatibility complex (MHC) genotype in the regulation of susceptibility to autoimmune diseases has been extensively studied in different populations, and certain HLA (the human MHC) alleles and haplotypes have been reported to be associated with several autoimmune diseases. In particular, the association with genes from the HLA-B8,DR3 haplotype has been reported by different research groups. This haplotype is associated in all Caucasian populations with a wide variety of diseases with autoimmune features, and in healthy subjects it is associated with a number of immune system dysfunctions. Mainly, peripheral blood mononuclear cells from HLA-B8,DR3-positive and -negative individuals differ in their ability to produce interleukin (IL)-2, IL-5, IL-12 and interferon-gamma upon stimulation with the mitogen phytohaemoagglutinin (PHA), while producing similar amounts of IL4, IL-6 and IL-10. Furthermore, in HLA-B8,DR3-positive subjects tumor necrosis factor alpha secretion is increased both with and without PHA stimulation. Accurate control of the functional repertoire of an immune response is a critical parameter in the response to infections as well as in immunopathology. MHC control of the class of the immune response at the level of cytokine production is a sophisticated way in which this occurs. This control might be involved in adaptive immune responses to infections as well as in immunopathology.
Cytokines Cell Mol Ther 1997 Dec
PMID:Modification of cytokine patterns in subjects bearing the HLA-B8,DR3 phenotype: implications for autoimmunity. 974 Mar 50

Macrophages are a major source of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), which are expressed during conditions of inflammation, infection, or injury. We identified an activity secreted by a macrophage tumor cell line that negatively regulates bacterial lipopolysaccharide (LPS)-induced expression of TNF-alpha. This activity, termed TNF-alpha-inhibiting factor (TIF), suppressed the induction of TNF-alpha expression in macrophages, whereas induction of three other proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-6, and monocyte chemoattractant protein 1) was accelerated or enhanced. A similar or identical inhibitory activity was secreted by IC-21 macrophages following LPS stimulation. Inhibition of TNF-alpha expression by macrophage conditioned medium was associated with selective induction of the NF-kappaB p50 subunit. Hyperinduction of p50 occurred with delayed kinetics in LPS-stimulated macrophages but not in fibroblasts. Overexpression of p50 blocked LPS-induced transcription from a TNF-alpha promoter reporter construct, showing that this transcription factor is an inhibitor of the TNF-alpha gene. Repression of the TNF-alpha promoter by TIF required a distal region that includes three NF-kappaB binding sites with preferential affinity for p50 homodimers. Thus, the selective repression of the TNF-alpha promoter by TIF may be explained by the specific binding of inhibitory p50 homodimers. We propose that TIF serves as a negative autocrine signal to attenuate TNF-alpha expression in activated macrophages. TIF is distinct from the known TNF-alpha-inhibiting factors IL-4, IL-10, and transforming growth factor beta and may represent a novel cytokine.
Mol Cell Biol 1998 Oct
PMID:Tumor necrosis factor alpha transcription in macrophages is attenuated by an autocrine factor that preferentially induces NF-kappaB p50. 974 85

Nutritional deficiency of zinc is widespread throughout the developing countries and a conditioned deficiency of zinc is known to occur in many diseased states. Zinc is known to play an important role in the immune system and zinc deficient subjects may experience increased susceptibility to a variety of pathogens. We have studied the effects of a mild deficiency of zinc on T cells in an experimental model of human zinc deficiency. We showed that T cell functions were affected adversely even when the deficiency of zinc was mild in humans. Characteristically during zinc deficiency, the serum thymulin activity (a thymic hormone) was decreased which was restored following zinc supplementation. Our studies also showed that zinc deficiency caused an imbalance between TH1 and TH2 functions. The production of IFN-g, IL-2, TNF-a (products of TH1 cells) were decreased, whereas the production of IL-4, IL-6 and IL-10 (products of TH2) were not affected during zinc deficiency. T cell subpopulation studies revealed that the CD4+ CD45RA+ to CD4+ CD45RO+ ratio was decreased as a result of zinc deficiency, suggesting that zinc may be required for the regeneration of new CD4+ T cells. We further documented that zinc deficiency decreased NK cell lytic activity and caused a decrease in the percentage of CD8+ CD73+ T cells which are known to be predominantly precursors of cytotoxic T cells. In a suitable cell culture model our studies revealed that the gene expression of a DNA synthesizing enzyme TK was affected adversely which resulted in delayed cell cycle and decreased cell growth. The above immunological consequences of zinc deficiency may be responsible for decreased cell mediated immune functions in zinc deficient subjects.
Mol Cell Biochem 1998 Nov
PMID:Zinc and immunity. 982 12

The dysregulation of cytokines is thought to play a role in the inflammatory and allospecific components of graft-versus-host disease (GVHD) and graft rejection (GR) post allogeneic bone marrow transplantation (BMT). Both complications occur post unrelated BMT at significantly higher frequencies than post BMT from identical sibling donors. The levels of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-10 and IL-12 following unrelated BMT were measured to examine cytokine dysregulation involvement in GVHD and GR. Of the 26 patients included in this study, 15 developed GVHD (14 acute; 1 acute and chronic), 5 had GR and 6 had uneventful BMT. TNF-alpha was markedly elevated in 13/15 of the patients with GVHD and in 3/5 patients with GR. IL-6 was elevated in patients with acute GVHD and with GR. IL-12 levels were similar in pre- and post-BMT sera. No correlation was found between HLA-C match and cytokine levels. In conclusion, a positive correlation was found between elevated levels of TNF-alpha, IL-6 and IL-10, and GVHD (p < 0.05, p < 0.005 and p < 0.002 respectively) and GR (p < 0.01).
Cytokines Cell Mol Ther 1998 Sep
PMID:Dysregulation of inflammatory cytokines in unrelated bone marrow transplantation. 982 41

Cytokines are important regulators of acute myelogenous leukemia (AML) blast proliferation. For a subset of patients the AML blasts show constitutive cytokine secretion and can undergo autonomous proliferation in vitro, whereas for other patients the blasts are dependent on exogenous cytokines for proliferation. The capability of autocrine proliferation is an adverse prognostic factor in AML. The three cytokines interleukin (IL)-4, IL-10 and IL-13 modulate in vitro blast proliferation, but the final effect of each cytokine (enhancement/inhibition/no effect) depends on differences between individual patients as well as the presence of other exogenous cytokines. In contrast to these divergent effects on blast proliferation, all three cytokines inhibit constitutive in vitro cytokine secretion by AML blasts. Because of the divergent effects on blast proliferation, it seems less likely that clinical therapy with these cytokines can be used to directly modulate AML blast proliferation. However, their effects on normal immunocompetent cells (and possibly the antigen-presenting capacity of AML blasts) are easier to predict. Thus direct (therapy with exogenous IL-4, IL-10 or IL-13) or indirect (enhancement of endogenous release of IL-4, IL-10 or IL-13) modulation of these cytokine effects on immunocompetent cells may become a useful clinical approach for enhancement of antileukemic immune effects. Such a modulation of immune reactivity can be used either as in vivo patient therapy or as manipulation of stem cell grafts prior to transplantation.
Cytokines Cell Mol Ther 1998 Sep
PMID:IL-4, IL-10 and IL-13 in acute myelogenous leukemia. 982 44


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