UNIPROT:P05231 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P05231 (interleukin-6)
23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between lymphocytes, cytokines, and endothelial cells (EC) is a key step in the inflammatory process. Interleukin-6 (IL-6) a pleiotropic cytokine in its effects, seems to be an early indicator of acute systemic inflammation. In this study, we have examined the effects of polyunsaturated fatty acids (PUFAs) on the production of IL-6 by human unstimulated EC or EC stimulated with TNF-alpha (100 U/ml); IL-4 (100 U/ml); LPS (1 ug/ml); or allogeneic peripheral blood lymphocytes (PBL). Twenty-four hour culture supernatants of immunoreactive IL-6 were measured by Sandwich ELISA. We have shown that the production of IL-6 was potentiated when EC were stimulated with TNF-alpha; IL-4; LPS; or monocyte-depleted PBL in comparison to unstimulated EC. The addition of n-3 PUFAs in culture medium (100 ug/ml DHA or EPA) significantly reduces the production of IL-6 by unstimulated EC; or stimulated with TNF-alpha; IL-4 pg/ml); LPS or depleted PBL respectively for DHA and EPA, whereas the n-6 PUFAs (Arachidonic acid), even used at the highest concentration, was ineffective. This inhibitory effect is PUFA dose dependent but is more potent with EPA than DHA. Regardless of the mode of action, since IL-6 is known to be involved in hematopoiesis, in the regulation of the immune response and in the inflammatory reaction, these results suggest that n-3 PUFAs may play a role in suppressing inflammation. Further studies are needed to elucidate the mechanism involved and the choice between the two fatty acids for clinical and therapeutic purposes.
...
PMID:Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6. 954 8

We have studied the expression of cytokines and viral genes induced by Newcastle disease virus (NDV) and Sendai virus in bone marrow-derived macrophages (BMM) and lymphocytes from C57BL/6 mice and the congenic line B6.C-H-28c. These mice carry the loci If-1h (high) or If-1l (low), respectively, that are responsible for up to tenfold differences in the interferon (IFN)-alpha, IFN-beta, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) response to NDV but not to Sendai virus. Only BMM but not spleen lymphocytes showed allele-specific differences in NDV-induced cytokine levels, indicating cell-specific If-1 expression. The If-1 locus harbors IFN-inducible gene(s) whose expression is prevented in the presence of cycloheximide. Our data provide evidence that the If-1l allele acts by specifically suppressing the cytokine response to NDV. Cytokine production was dependent on infectious virions, and kinetic analyses revealed a close correlation between the amount of viral transcripts and individual cytokine mRNA. BMM from lf-1l mice strongly restricted transcription of the NDV nucleoprotein (NP) gene, whereas BMM from If-1h mice supported NP transcription. Following treatment with IL-4, which inhibited constitutive IFN-beta gene expression, however, If-1l BMM became highly permissive for transcription of the viral NP gene and released high amounts of cytokines. We conclude that If-1l gene products are responsible for the low producer phenotype by efficiently interfering with NDV transcription, leading to strongly reduced intracellular levels of cytokine inducing viral dsRNA intermediates.
...
PMID:Interferon-induced expression of If-1h and If-1l alleles in Newcastle disease virus-infected mouse macrophages is associated with specific differences in viral gene transcription. 955 81

The plasma levels of HIV-1 RNA, tumor necrosis factor alpha (TNF-alpha), soluble receptors type II of TNF-alpha (sTNF-alpha RII), soluble receptors of interleukin-4 (sR IL-4), interleukin-6 (IL-6), soluble receptors of interleukin-6 (sR IL-6), granulocyte macrophage colony stimulating factor (GM-CSF), soluble receptors of GM-CSF (sR GM-CSF), RANTES, MIP-1 alpha and MIP-1 beta were measured in 80 HIV-infected patients. All patients had not been treated previously with antiretroviral drugs and did not present a recent history of opportunistic infection. A statistically significant correlation was found between HIV-1 RNA and TNF-alpha (p = 0.005) or sTNF-alpha RII levels (p < 0.001). RANTES and MIP-1 alpha levels did not correlate with HIV-1 RNA. MIP-1 beta levels were correlated with plasma RNA titers in patients with CD4+ T cells < 200 x 10(6)/l (p = 0.03). MIP-1 alpha and sR IL-4 levels were significantly different according to the CD4+ T cell range (p = 0.003 and p = 0.0002, respectively). GM-CSF and sR GM-CSF were undetectable in each case. These data confirm that HIV-1 replication in the plasma is correlated with TNF-alpha levels, but do not show a clear correlation with levels of the chemokines studied.
...
PMID:Correlation between plasma levels of cytokines and HIV-1 RNA copy number in HIV-infected patients. 956 79

The 70-kDa recombinant Candida albicans heat shock protein (CaHsp70) and its 21-kDa C-terminal and 28-kDa N-terminal fragments (CaHsp70-Cter and CaHsp70-Nter, respectively) were studied for their immunogenicity, including proinflammatory cytokine induction in vitro and in vivo, and protection in a murine model of hematogenous candidiasis. The whole protein and its two fragments were strong inducers of both antibody (Ab; immunoglobulin G1 [IgG1] and IgG2b were the prevalent isotypes) and cell-mediated immunity (CMI) responses in mice. CaHsp70 preparations were also recognized as CMI targets by peripheral blood mononuclear cells of healthy human subjects. Inoculation of CaHsp70 preparations into immunized mice induced rapid production of interleukin-6 (IL-6) and tumor necrosis factor alpha, peaking at 2 to 5 h and declining within 24 h. CaHsp70 and CaHsp70-Cter also induced gamma interferon (IFN-gamma), IL-12, and IL-10 but not IL-4 production by CD4+ lymphocytes cocultured with splenic accessory cells from nonimmunized mice. In particular, the production of IFN-gamma was equal if not superior to that induced in the same cells by whole, heat-inactivated fungal cells or the mitogenic lectin concanavalin A. In immunized mice, however, IL-4 but not IL-12 was produced in addition to IFN-gamma upon in vitro stimulation of CD4+ cells with CaHsp70 and CaHsp70-Cter. These animals showed a decreased median survival time compared to nonimmunized mice, and their mortality was strictly associated with organ invasion by fungal hyphae. Their enhanced susceptibility was attributable to the immunization state, as it did not occur in congenitally athymic nude mice, which were unable to raise either Ab or CMI responses to CaHsp70 preparations. Together, our data demonstrate the elevated immunogenicity of CaHsp70, with which, however, no protection against but rather some enhancement of Candida infection seemed to occur in the mouse model used.
...
PMID:A 70-kilodalton recombinant heat shock protein of Candida albicans is highly immunogenic and enhances systemic murine candidiasis. 957 2

Previous studies by our group have demonstrated that in vitro exposure to delta-opioid receptor agonists results in a significant immunostimulation, whereas in vitro exposure to non-peptidic delta-opioid receptor antagonists results in significant suppression of various immune functions. The present study assessed potential immunomodulation by the peptidic delta-opioid receptor antagonists TIPP, D-TIPP, and ICI 174864 using a panel of in vitro immune function assays. Splenocytes from female B6C3F1 mice were cultured with the peptides at concentrations of 0.00001-10 microM. B cell proliferation was quantified following cellular activation, T cell function was assessed by cytokine production following stimulation with anti-CD3 monoclonal antibody, natural immunity was assessed by quantitating natural killer (NK) cell activity following a 24-h exposure, and macrophage function was assessed by quantification of interleukin-6 (IL-6) production. None of the peptides examined significantly affected B cell proliferation. Production of IL-2 by T cells was not consistently affected by exposure to either TIPP or D-TIPP, but was significantly suppressed at 10 microM ICI 174864. Production of IL-4, however, was significantly suppressed by low concentrations of either TIPP or D-TIPP, and by 10 microM ICI 174864. IL-6 production by macrophages was unaffected except for sporadic incidents of enhanced production in cells exposed to ICI 174864. NK cell function exhibited a differential pattern of suppression, with the greatest degree of suppression observed following exposure to TIPP and only slight suppression in cells exposed to either D-TIPP or ICI 174864. These data suggest that peptidic delta-opioid receptor antagonists do not exhibit the same pattern or degree of immunosuppressive activity as the non-peptidic antagonists at equivalent in vitro concentrations.
...
PMID:In vitro exposure to peptidic delta opioid receptor antagonists results in limited immunosuppression. 957 44

We have examined the contribution of endogenous interleukin-6 (IL-6) to the differentiation of murine B-cell hybridomas. AT73 was established by somatic hybridization between BALB/c mice B cells and 2.52M, a hypoxanthine-aminopterine-thymidine (HAT) medium-sensitive B-cell line mutant. It spontaneously secreted IgM, and addition of exogenous IL-6 augmented IgM secretion. Triggering of CD40 led to an augmentation of IL-6 expression and IgM secretion. Blocking the binding of IL-6 to its cellular receptor through the use of inhibitory monoclonal antibodies inhibited CD40-induced IgM secretion, suggesting a possible autocrine role of IL-6 for the differentiation of a CD40-activated B-cell hybridoma. Co-triggering with CD40 and B-cell receptor or activation through CD40 and IL-4 led to a synergistic augmentation of IL-6 expression as well as additive IgM secretion; this was followed by a marked decrease in the expression of B-cell surface markers on the cell membrane. Furthermore, under conditions where IL-6 expression was augmented, gp80 expression was down-regulated, suggesting a negative feedback mechanism in this B-cell hybridoma. These findings provide a role by which T-cell-dependent activation through CD40 regulates an IL-6 autocrine loop, controlling B-cell differentiation.
...
PMID:Regulation of interleukin-6 and interleukin-6R alpha (gp80) expression by murine immunoglobulin-secreting B-cell hybridomas. 965 21

In this study, granulocyte colony-stimulating factor (GCSF) proteins were chosen as subjects for normal mode analysis. As helical cytokines with a four helix bundled type topology, they were classified into long chain and short chain groups by Sprang and Bazan. Normal mode calculations were also carried out with leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and growth hormone (GH) as members of the long chain group and GCSF and IL-2 and IL-4 as members of the short chain group. For the GCSF families it was found that the fluctuations in the helical region are smaller than in the loop region, and it is clear that on the whole the smaller fluctuation residues belong to a large hydrophobic core region. Thus, it can be imagined how the receptor binding sites approach the receptor within the normal time-scale of pico seconds. In addition, two similar domain-type motions in low frequency modes were found with proteins in the long chain group, although we never observed any sequence similarity in the two separate two-domain regions in each protein of the long chain group. On the other hand, these two domain-type motions were not clear in proteins of the short chain group.
...
PMID:Dynamic structures of granulocyte colony-stimulating factor proteins studied by normal mode analysis: two domain-type motions in low frequency modes. 969 16

Interleukin-6 (IL-6) is a pleotropic cytokine implicated in the pathogenesis of local inflammation during viral upper respiratory infections. This study determined if experimental influenza A virus infection causes local IL-6 production. Seventeen healthy, adult subjects were intranasally inoculated, by course drops, with a safety-tested strain of influenza A/Kawasaki/86 (H1N1) virus. Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed once before and then daily for 8 days after the virus inoculation. Lavage samples were submitted for virus culture and were examined for IL-6 and IL-4 by enzyme-linked immunosorbent assay. The IL-6, but not IL-4, levels were significantly increased in the nasal lavage samples of the 12 subjects who shed virus but not in those of the 5 subjects who did not shed virus. Moreover, the elevations in IL-6 levels were related temporally to the development of nasal symptoms and secretions but not to systemic symptoms. These results suggest a role for locally produced IL-6 in the pathogenesis and expressed symptomatology of influenza A virus infection.
...
PMID:Increased interleukin-6 levels in nasal lavage samples following experimental influenza A virus infection. 972 23

Sixty six patients with non-Hodgkin's lymphomas (NHL) were studied, interleukin-6 (IL-6) was revealed in the blood sera of 33 patients. IL-6 was revealed more frequently in patients with high-grade malignant (p < 0.05) than in those with low-grade malignancy. The largest group of IL-6 positive patients included NHL patients with diffuse large B-cell lymphoma and angioimmunoblastic lymphoma. The marked relationship was found between the serum IL-6 levels and the stage of disease: the serum IL-6 level was significantly lower in untreated patients with Stages II and III disease than in those with end-stage (IV) NHL. IL-6 significantly decreased upon remission, comparable with its level before the initiation of treatment. Analysing the association of prognosis of disease with the serum IL-6 showed that in the group of patients with good (The SNLG index < 2) and intermediate (2 < SNLG index < by 2.6) prognosis, the concentration of this cytokine was significantly lower than in those with poor prognosis (SNLG index > 2.6). There was a significant decrease of the total survival rates of NHL with serum IL-6 found. Therefore, IL-6 is a good prognostic marker in NHL and associated with the activity of a malignant process. Additionally, the increased serum IL-6 levels correlated with NK activities positively and with serum IL-4 levels negatively.
...
PMID:[Diagnostic and prognostic value of interleukin-6 in malignant non-Hodgkin's lymphomas]. 984 10

It has been demonstrated that endogenous cytokines including gamma interferon (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) play protective roles but that IL-4 and IL-10 play detrimental roles in nonlethal Listeria monocytogenes infection in mice. In this paper, we studied the roles of endogenous cytokines in a lethal infection with L. monocytogenes in mice. TNF-alpha and IL-6 titres in the bloodstreams, spleens and livers paralleled bacterial numbers in the organs, and both these cytokines and the bacterial numbers peaked just before the mice died. The high titres of TNF-alpha notably detected in the circulation in lethal infection were different from those in nonlethal infection. The maximum production of IFN-gamma was observed before the peaks of TNF-alpha and IL-6, and IFN-gamma almost disappeared from the bloodstreams and organs just before the mice died. No notable difference of IFN-gamma titres between lethal infection and nonlethal infection in the specimens obtained from mice was observed. IL-10 was also detected in the bloodstreams earlier than the peaks of TNF-alpha and IL-6 during lethal infection, while IL-4 was never detected in the sera. The administration of monoclonal antibodies (mAbs) against TNF-alpha, IFN-gamma, IL-6, IL-4 or IL-10 failed to rescue mice from lethal L. monocytogenes infection, whereas anti-TNF-alpha mAb and anti-IFN-gamma mAb prevented mice from lethality by high-dose endotoxin shock. These results suggest that lethality in L. monocytogenes infection might not be determined solely by these cytokines.
...
PMID:Endogenous cytokines during a lethal infection with Listeria monocytogenes in mice. 1036 18

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