Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following reverse transcription and PCR amplification, the human interleukin-6 (IL-6) cDNA was cloned from total RNA of activated human tonsillar mononuclear cells. Southern blot showed the presence of specific band, and its DNA sequence demonstrated that the fragment was 650 bp in length, spanning the complete coding region and part of 5' and 3'-untranslated regions. The human IL-6 sequence seemed to be well conserved. One nucleotide change at 429 position was observed, but this change did not affect the amino acid composition. After inserting the cloned cDNA into retroviral vector XM-6, the recombinant was packaged in PA317 cells and the amphotropic virus titer reached 5 x 10(5) CFU/ml. Human IL-6 was expressed in mammalian cell line SP2/0 cells, after being infected by the constructed retrovirus. The G418 resistant SP2/0 cells secreted IL-6. Its supernatant was able to maintain in vitro growth of the IL-6 dependent T1165 cell line. Northern blot analysis of the transfected SP2/0 cells showed significantly elevated IL-6 message, being consistent with the result of T 1165 bioassay. The expression was stable during the 12 month period of observation. The hybridoma cells, formed after fusion of the transfected SP2/0 cells and lymphocytes, exhibited accelerated growth.
Zhonghua Zhong Liu Za Zhi 1992 Sep
PMID:[Stable and efficient expression of human interleukin-6 cDNA in mammalian cells after gene transfer]. 129 Dec 90

This study was undertaken to evaluate the effect of a cyclooxygenase inhibitor, ibuprofen, at various time intervals in a live Escherichia coli model of canine septic shock. Group I (control) animals (n = 5) received a LD100 dose of 10(9) live E. coli per kilogram were given no further treatment. Group II animals (n = 5) received a 10 mg/kg bolus of ibuprofen 10 min prior to bacterial infusion. Group III animals (n = 5) received ibuprofen 15 min after the bacterial infusion. Statistical analysis revealed the following: Group II animals had significantly higher MABP and significantly lower levels of serum fluorescent products (superoxide radical activity), plasma thromboxane B2, prostaglandin E2, and endotoxin levels compared to Group I animals (P less than 0.05). Plasma levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were significantly elevated (P less than 0.05) from baseline in all animals (Groups I, II, and III), but ibuprofen treatment failed to either increase or decrease these levels. This study demonstrates that ibuprofen treatment can significantly reverse the deleterious hemodynamic and metabolic effects commonly seen in live E. coli septic shock without depressing the endogenous production of TNF or IL-6. These data support the hypothesis that sepsis initiates a cascade of mediators with the cytokines TNF and IL-6 being proximal events which in turn stimulate the next level, with ibuprofen probably exerting its inhibitory effect distal to this point in the cascade.
J Surg Res 1992 Sep
PMID:Ibuprofen intervention in canine septic shock: reduction of pathophysiology without decreased cytokines. 132 83

Nitric oxide (NO), apart from its properties as a vasodilator, is a cytotoxic agent released from macrophages upon stimulation with immunomodulating agents such as interferon-gamma and endotoxin. In rat Kupffer cells endotoxin causes the release of NO as well as of tumor necrosis factor-alpha and prostaglandin E2 (PGE2). This eicosanoid and its second messenger, cyclic AMP, have been shown to increase nitric oxide formation in Kupffer cells treated with endotoxin (Gaillard et al. (1991) Pathobiology 59, 280-283). But not only added PGE2 but also the prostaglandin produced endogenously upon stimulation with endotoxin increases NO synthesis. Neither tumor necrosis factor-alpha nor interleukin-1 beta stimulate NO synthesis by themselves, but together with PGE2 they are as effective as lipopolysaccharide plus PGE2. To replace PGE2 in the combination with the cytokines, however, dibutyryl cAMP has to be present in higher concentrations than with LPS. Interleukin-6 alone or in combination with PGE2 or dibutyryl cAMP is without any effect. Anti-TNF-alpha as well as anti-PGE2 antibodies reduce the release of NO upon stimulation with LPS. Consequently, the effect of LPS on NO production seems to be in part due to the self-stimulating effect of PGE2 and some cytokines, both produced by Kupffer cells upon LPS stimulation.
Biol Chem Hoppe Seyler 1992 Sep
PMID:Regulation by prostaglandin E2 of cytokine-elicited nitric oxide synthesis in rat liver macrophages. 133 72

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells. IL-4 and IL-6 increased significantly EBV-B cell proliferation after 3 and 5 days of culture, where IL-2 had no effect. The effect of IL-4 and IL-6 on EBV-B cells was abolished after pre-incubation with anti-IL-4 and anti-IL-6 neutralising antisera, respectively. TPA induced a dose dependent inhibition of proliferation both in serum free and 10% fetal calf serum (FCS) supplemented culture medium. Combinations of TPA and interleukins did not restore lymphoblastoid cell proliferation to background levels. All possible combinations of the three cytokines showed no synergistic or antagonistic effect on proliferation. TPA induced significant phenotypic changes of EBV immortalised B lymphocytes, by increasing IL-2 receptor (IL-2R) expression and decreasing CD20 and CD23 antigen expression. Other B cell differentiation antigens; HLA-DR, CD19, and transferrin receptor (CD71), did not demonstrate significant changes. A dose dependent inhibition of CD21 and increase in CD22 expression was observed in 2 out of 3 lymphoblastoid cell lines tested.
Leuk Lymphoma 1992 Sep
PMID:Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes. 133 96

We have studied the excessive deposition of extracellular matrix in a patient with fibrolamellar carcinoma of the liver. The collagen matrix was predominantly composed of collagens I, III, and V. Since specific mRNAs for collagens I and III were detected by in situ hybridization, we also provide evidence that the fibroblastoid stromal cells were the major source of this collagen. Occasionally, also tumor cells could be shown to express collagen III-mRNA. Furthermore, some tumor cells showed positive signals for TGF-beta 1, while isolated stromal cells expressed interleukin-6. This cytokine expression may probably be related to the altered control of collagen gene expression.
Mod Pathol 1992 Sep
PMID:Excessive collagen formation in fibrolamellar carcinoma of the liver: a morphological and biochemical study. 841 1

1. The authors developed a primary culture technique for neuronal cells from postnatal rat brains and studied the effects of neurotrophic factors on the naturally developed neurons. 2. We demonstrated changes in the neurotrophic role of nerve growth factor (NGF) during the developmental stages of the rat: NGF was shown to act as a differentiation factor in the early stages and as a survival factor later. 3. It appeared that interleukin-6 (IL-6) supported the survival of septal cholinergic neurons obtained from 10-day-old rats. IL-6, however, did not induce the differentiation of embryonic rat septal cholinergic neurons. IL-6 improved the survival of mesencephalic catecholaminergic neurons from postnatal and embryonic rat brains, which have known not to be response to NGF.
Prog Neuropsychopharmacol Biol Psychiatry 1992 Sep
PMID:Culture of neuronal cells from postnatal rat brain: application to the study of neurotrophic factors. 135 95

Only a minority of T cells at cell-mediated immune lesions are antigen specific. In the lesions of human autoimmune disease, such as the synovial membrane in rheumatoid arthritis, the T cells are activated as shown by a variety of phenotypic and functional changes including the expression of HLA-DR and the production of interleukin-6 (IL-6). The stimulatory pathway involved is unknown but does not seem to involve the T-cell receptor. Alternative pathways of activation which may be involved include the CD2 molecule. It is shown that the formation of sheep red blood cell (SRBC) rosettes with resting T cells from human peripheral blood, which is equivalent to CD2/LFA-3 binding, leads to the de novo transcription of the HLA-DR and IL-6 genes and the expression of HLA-DR on the surface of the T cells. There was no transcription of the interleukin-2 (IL-2) or the interleukin-2 receptor (IL-2R) genes and Tac expression was not seen. The rosetted T cells did not proliferate. These are all characteristics of T cells at chronic inflammatory sites. It is concluded that receptor-ligand interactions between CD2/LFA-3, which are expressed in increased amounts in the rheumatoid joint, may be one pathway by which antigen non-specific T cells are recruited as effector cells in lesions of human autoimmune disease.
Scand J Immunol 1992 Sep
PMID:Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via the CD2 molecule: relevance to chronic immune-mediated inflammation. 135 12

There is currently accumulating evidence for bidirectional communication between the neuroendocrine and immune systems. Various cytokines have been suggested to be involved in the stimulation of stress hormone secretion during the times of infection and inflammation. To assess the possible involvement and pathophysiologic significance of cytokines in the mechanisms responsible for the perioperative stress response of the hypothalamo-pituitary-adrenal axis, we observed the changes of plasma adrenocorticotropic hormone and cortisol levels together with those of plasma endotoxin and cytokine levels. In patients undergoing pancreatoduodenectomy, perioperative stimulation of adrenocorticotropic hormone and cortisol secretion was accompanied by a significant elevation of plasma cytokine levels. Application of epidural block up to the upper thoracic levels failed to suppress this stress response effectively. In patients undergoing unilateral total hip replacement, the response of plasma hormone levels was smaller and briefer with no significant increase of plasma cytokine levels. Application of epidural block up to the lower thoracic levels suppressed this hormonal response almost completely. In patients undergoing pancreatoduodenectomy, a significant elevation of plasma endotoxin level was followed by a gradual but significant elevation of plasma tumor necrosis factor alpha and interleukin-6 levels. It seems likely that the stimulatory effects of these cytokines on the secretion of adrenocorticotropic hormone and cortisol might be involved in the development of the greater and more prolonged stress response of hypothalamo-pituitary-adrenal axis. Our present study suggests that not only neural input from the surgical wound but also stimulation of cytokine production were responsible for the development of the stress response of the hypothalamo-pituitary-adrenal axis during and after upper abdominal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesiology 1992 Sep
PMID:Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery. 846 81

Thyroid cells are exposed to complement attack in Graves' disease and Hashimoto's thyroiditis, but are resistant to killing by homologous complement. We have examined the effects of sublethal complement attack on thyroid cells in vitro. Extracellular reactive oxygen metabolites were produced and prostaglandin E2, interleukin-1 alpha, and interleukin-6 were released after complement attack. Cells pretreated with interferon-gamma and interleukin-1 alpha, which increase expression of CD59, were more resistant to these effects of complement. Conversely, blockade of CD59 with monoclonal antibody increased complement-mediated oxygen radical production and release of prostaglandin E2, interleukin-1 alpha, and interleukin-6. The antithyroid drugs methimazole and propylthiouracil abolished or reduced oxygen radical production by complement-attacked thyroid cells and reduced cytokine release. These results suggest that sublethal complement attack in autoimmune thyroid diseases exacerbates tissue injury by causing thyroid cells to release potent phlogistic mediators, although some degree of protection may be afforded in vivo by cytokine-mediated upregulation of CD59. Antithyroid drugs, concentrated within thyroid cells, will prevent the release of these inflammatory molecules, which may in turn explain the amelioration of thyroiditis and remission of Graves' disease after such treatment.
Lancet 1992 Sep 12
PMID:Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells. 138 Oct 35

During the progression of Mg deficiency in a rodent model, we have observed dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk on a Mg-deficient diet. Sequential analyses of these cytokine changes in the serum of rats revealed an initial rise at day 12, followed by a major elevation in all three cytokine levels by day 21. Of greater interest was an early peak in the serum level of the neuropeptide substance P after only 5 days on the diet. This "neuronal" tachykinin is thought to be released from neural tissues, and it is known to stimulate production of certain cytokines, including IL-1, IL-6, and TNF-alpha. In addition, there was a concomitant increase in histamine levels, which may have resulted from stimulation and degranulation of mast cells by substance P. Thus we hypothesize that the release of substance P may be the earliest pathophysiological event leading to stimulation of the inflammatory cytokines, which may then stimulate the free radical mechanisms of injury previously confirmed by our work.
Am J Physiol 1992 Sep
PMID:Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis. 138 53


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