Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further understand the role of cytokine responses in symptom formation and host defenses in influenza infection, we determined the levels of IL-1beta, IL-2, IL-6, IL-8, IFN-alpha, TGF-beta, and TNF-alpha in nasal lavage fluid, plasma, and serum obtained serially from 19 volunteers experimentally infected with influenza A/Texas/36/91 (H1N1) and correlated these levels with various measures of infection and illness severity. We found that IL-6 and IFN-alpha levels in nasal lavage fluids peaked early (day 2) and correlated directly with viral titers, temperature, mucus production, and symptom scores. IL-6 elevations were also found in the circulation at this time point. In contrast, TNF-alpha responses peaked later (day 3 in plasma, day 4 in nasal fluids), when viral shedding and symptoms were subsiding. Similarly, IL-8 peaked late in the illness course (days 4-6) and correlated only with lower respiratory symptoms, which also occurred late. None of IL-1beta, IL-2, or TGF-beta levels increased significantly. These data implicate IL-6 and IFN-alpha as key factors both in symptom formation and host defense in influenza.
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PMID:Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. 944 98

Immunoglobulin E plays a central role in the pathogenesis of allergic diseases. Therefore an understanding of mechanisms which regulate production of IgE is very important. Recent studies have demonstrated that the induction of IgE synthesis in B cells requires two signals. The first one, IgE isotype-specific, is delivered by interleukins 4 or 13 and results in epsilon germ line transcription. The second B-cell-activating factor is responsible for switch recombination and expression of mature epsilon RNA transcripts. This signal is delivered by lymphocytes T, but these cells can be replaced by Epstein-Barr virus infection, protein gp39 (CD40L), monoclonal antibodies to CD40 and CD58, membrane-TNF-alpha, as well as corticosteroids. Besides this a variety of factors can modulate the IgE synthesis. Interleukin-2, -5, -6, -9, -10, MIP1-alpha, RANTES and sCD23 enhance the production of IgE whereas PAF, PGE2, IL-8, -12 and 18, IFN-alpha and gamma, TGF-beta, sIL-4R, IL-1Ra, and probably sIL-1R inhibit it. In this article, we review current knowledge about the mechanisms underlying the synthesis of IgE in humans, including molecular events and clinical attempts at reduction of the total IgE level in patients with allergic diseases.
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PMID:[Regulation of immunoglobulin E synthesis]. 948 97

Various interferon-alpha (IFN-alpha) preparations, either as individual subtypes or natural mixtures, induce or inhibit expression of several other cytokines, as well as cytokine receptors and chemokines. The cytokines and receptors reportedly affected by IFN-alpha include interleukin-1 (IL-1), IL-2, IL-6, IL-8, IL-1 receptor, IL-1 receptor antagonist, tumor necrosis factor, tumor necrosis factor receptor, and IFN-gamma, all of which may amplify the effects of IFN-alpha treatment. The mechanism by which IFN-alpha induces expression of these cytokines is not clear. Some of the therapeutic and toxic effects associated with IFN-alpha therapy may be caused by the induction or inhibition of other cytokines and their respective cellular effects. Side effects including fever, anorexia, and fatigue can be caused by one or more of the cytokines induced by IFN-alpha. The response of different cell types, normal or malignant, to cytokines can vary. Such variation in cell type-specific responses may contribute to the diverse array of physiologic effects associated with IFN-alpha therapy. Further research is required to systematically uncover how other cytokines, receptors, or cellular factors contribute to the therapeutic and toxic effects of IFN-alpha.
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PMID:The effects of interferon-alpha on the production and action of other cytokines. 948 37

The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.
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PMID:Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages. 949 13

The efferent lymph duct of the ovine prescapular lymph node was cannulated, and Salmonella abortusovis (SAO), a specific pathogen for sheep inducing abortion and mortality of newborn lambs, was inoculated by the subcutaneous route in this lymph node drained area. While the prescapular lymph node draining the inoculation site represented an efficient barrier for the vaccinal SAO Rv6 strain spreading, SAO 15/5 virulent bacteria were steadily detected in efferent lymph of infected sheep. The inoculation of the virulent strain of SAO induced a greater increase of the cell output than did the attenuated vaccinal strain, but proportions of blast cells appearing in the efferent lymph were similar in both cases. Flow cytometry analysis showed that B and T cell outputs were both increased during SAO infections, but while T cell subset proportions slightly decreased, B cell percentages significantly rose, and, at the peak response, almost all of the lymphoblast cells were activated B cells. Typical antibody profiles characteristic of a primary immune response were observed, and antibody titres were greater in the efferent lymph of animals inoculated with the virulent strain of SAO. Many of the cytokine mRNAs we investigated were steadily detected by RT-PCR in efferent lymph cells of control sheep, but frequencies of detection of IL-2, IFN gamma, IL-1 beta and TNF alpha mRNAs were augmented in efferent lymph cells following inoculation of both SAO virulent or vaccinal strains. IL-10 and IL-8 mRNAs could only be detected after a SAO inoculation, while detection of IL-4 mRNAs was increased only in efferent lymph cells from SAO virulent strain-infected sheep. The efferent lymph cannulation technique thus appeared a very powerful way to study the in vivo development of the immune response to SAO, in its natural host, the sheep.
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PMID:Analysis of the immune response in sheep efferent lymph during Salmonella abortusovis infection. 953 71

Here, we report the molecular regulation of interleukin (IL)-8 expression in human melanoma cells. The inflammatory cytokines IL-1beta and tumor necrosis factor-alpha (TNF-alpha) up-regulated IL-8 expression, in a time- and concentration-dependent manner, in three metastatic melanoma variants, SBC-2 (nonmetastatic), A375P (low metastatic), and A375SM (high metastatic), by increased transcription of the IL-8 gene, leading to increased levels of IL-8 mRNA and protein production. Furthermore, we report that IFN-alpha and IFN-beta did not inhibit steady-state IL-8 production. However, IFN-alpha and IFN-beta inhibited IL-1beta or TNF-alpha-mediated up-regulation of IL-8 mRNA. In addition, IFN-beta demonstrated a more potent inhibitory effect at a lower concentration than did IFN-alpha. Both pretreatment and simultaneous treatment of melanoma cells with IFN-alpha or IFN-beta inhibited the IL-1beta and TNF-alpha up-regulation of IL-8 mRNA levels. This inhibition was at the transcriptional levels and was unaffected by a protein synthesis inhibitor, suggesting that this did not require de novo protein synthesis. Further, modulation of IL-8 levels by IL-1beta, alone or in combination with IFN-beta, affected the proliferation of melanoma cells. In summary, our data suggest that the up-regulation of IL-8 expression in melanoma cells is regulated at the transcriptional level and is rapidly and specifically inhibited by IFN-alpha or IFN-beta, independent of de novo protein synthesis, perhaps due to a transient modification of a preexisting factor(s).
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PMID:Regulation of interleukin 8 expression in human malignant melanoma cells. 953 60

The intestinal epithelial cell population is comprised of a dynamic continuum, ranging from undifferentiated, actively proliferating crypt cells, to mature absorptive villus enterocytes, lacking mitotic capacity. Under normal conditions, the constant loss of differentiated villus tip cells via apoptosis leads to a complete renewal of the epithelial cell population every few days. The physiological factors regulating enterocyte proliferation, maturation and apoptosis in health, as well as those that modulate these events in disease states remain largely unknown. It has been demonstrated in vitro that immature crypt cell proliferation is stimulated by factors such as TGF alpha and TNF alpha, whereas TFG beta and IFN gamma inhibit mitotic activity. Further studies showed that intestinal epithelial cells are able to produce and secrete several cytokines such as IL6, IL8, TNF alpha, TGF alpha and TGF beta, indicating the potential for autocrine and paracrine responses. A variety of immune mediated bowel disorders, including celiac disease, Crohn's disease and ulcerative colitis, are characterized by accelerated epithelial cell turnover and apoptosis, leading to altered crypt/villus morphology. There is increasing evidence that these changes, and the accompanying functional alterations of the bowel epithelium, are mediated by the cytokines released from infiltrating inflammatory cells, as well as from enterocytes themselves in an autocrine fashion.
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PMID:Cytokine--intestinal epithelial cell interactions: implications for immune mediated bowel disorders. 955 84

IL4 has been shown to differentially modulate HIV1 replication in primary cells of the monocyte/macrophage lineage. Its effects on chronic HIV1 infection, however, are unknown. To address IL4-mediated effects on promonocytic cells chronically infected with HIV1, U1 cells were incubated in the presence or absence of IL4 together with cytokines that are known to induce both HIV1 and IL8 expression. IL4 enhanced IL1 beta-induced HIV1 and IL8 expression in promonocytic U1 cells, whereas it suppressed their expression induced by cytokines IL6, GM-CSF and to a small extent, TNF alpha. IL4 suppressed IFN gamma-induced IL8 production with increasing IL4 concentration, while HIV1 p24 core antigen production was suppressed at low IL4 input (0.1 and 1 U/ml) but was substantially enhanced at a high IL4 input concentration (10 U/ml). Results showed that the immunosuppressive cytokine IL4 can behave variably in modulating HIV1 and IL8 expression, depending on both the inducing cytokine and the input concentration of IL4.
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PMID:Interleukin-4 regulation of cytokine-induced HIV1 and interleukin-8 expression in promonocytic U1 cells is concentration- and cytokine-dependent. 956 61

Dysfunction of cytokine secretion pattern has been suggested to play a central role in the immunopathogenesis of HIV infection. In fact a shift of T helper cell functions from a Th1-type to TH0- or TH2-type has been observed in HIV-1 infected subjects undergoing disease progression. The inhalance of cytokine network is accompanied by persistent activation of the immune system, impaired ability to mount a proper activation response (anergy), and priming to apoptosis. Extensive investigation during the last decade has been conducted on the influence of HIV-1 gp120 or of its precursor gp160 on several lymphocyte and monocyte functions. Gp120 is able to rise intracellular calcium concentration and to induce the formation of inositol triphosphate, can block mitogen- or antigen-driven T cell activation, can induce altered cytokine production by activated PBMC subpopulations, determines impaired cytotoxicity and chemotactic response to antigens, interferes with the activity of antigen presenting cells, enhances or induces apoptosis, stimulates polyclonal B cell activation and induces or up-modulates a number of cytokines, including IL-6. TNF, IL-1-alpha and -beta, IL-10 and IL-8. Furthermore, both IFN-alpha and -gamma, as well as several markers of IFN activity, such as beta 2-microglobulin and neopterin, are induced in gp120-stimulated PBMC. However, neither IL-4 (Th2-type) nor IL-2 (Th1-type), nor DNA synthesis are activated by gp120. On the other hand gp120-stimulated PBMC express increased IL-2 receptors, and can be induced by exogenous IL-2 to proliferate, suggesting that they are in a state of at least partial activation. According to this hypothesis, other activation markers, both early (such as CD69), and late (such as CD45RO and CD71), are induced by gp120, but this even partial activation does not lead to the ability of PBMC to support productive infection by HIV-1, unless in the presence of exogenous IL-2. The HIV-induced cytokines can influence HIV infection either directly, by up- or down-modulating virus replication, or indirectly, by modulating the expression of cellular molecules. In fact, during the budding process, the HIV envelope captures a number of cell membrane proteins, including cytokine receptors such as IL-2R, adhesion molecules such as LFA-1, ICAM-1, -2, HLA Class I and II, as well as cell lineage markers. Gp120-induced cytokines, particularly IFN-gamma, upmodulate the cellular expression of intercellular adhesion molecules, such as ICAM-1. We have shown that the IFN-gamma-driven increase of the expression of ICAM-1 by cells chronically infected with HIV-1 can be transmitted to the virus progeny, resulting in phenotypic alteration of the virus, and leading to the expansion of its host cell spectrum to CD4-negative cells expressing the appropriate ligands, i.e. LFA-1. Intercellular adhesion molecules are also involved in the cell-mediated transmission of HIV infection, and the increased ICAM-1 expression induced by IFN-gamma determines a stimulation of the transmission of HIV from abortively infected endothelial cells to permissive CD4 lymphocytes. On the whole, these data indicate that HIV, or its soluble products such as gp120, can modify several PBMC functions, by inducing a number of cytokines and a partial state of immune activation. It is possible that the gp120-driven changes of PBMC functions are not only an epiphenomenon of HIV infection, but rather, it is likely that they can participate in the immunopathological events responsible for disease progression.
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PMID:Induction of lymphomonocyte activation by HIV-1 glycoprotein gp120. Possible role in AIDS pathogenesis. 960 76

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.
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PMID:IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon. 963 33


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