Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:021712 (IL-6)
 58,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fusidic acid and its sodium salt (fusidin) are anti-staphylococcal drugs. In vitro studies have shown that they prevent the lymphocyte co-stimulatory activities of the cytokines IL-1 and IL-6 in a manner similar to that of cyclosporin A, and prevent the inhibitory effect of IL-1 on glucose-induced insulin production. As IL-1 and IL-6 are thought to play a role in the pathogenesis of Type 1 diabetes, the aim of this study was to investigate whether fusidin could influence the disease incidence of the spontaneously diabetic BB rat model. Accordingly, a group of 50 BB rats receiving fusidin dissolved in their drinking water were compared to a control group of 55 rats over a period of 200 days. The incidence of diabetes was found to be 52% in the experimental group and 71% in the control group (P < 0.05). The degree of insulitis and the number of islets at histological examination were similar among the non-diabetic animals whereas the diabetic fusidin-treated animals showed a higher degree of islet preservation than the diabetic control rats. The results are highly indicative of an anti-diabetogenic effect of fusidin.
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PMID:Anti-diabetogenic effect of fusidic acid in diabetes prone BB rats. 130 76

Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NIN), a traditional Chinese medicine, is a drug made of spray-dried powder of hot water extract obtained from twelve species of medical plants. An intraperitoneal (ip) injection with NIN 2 days before intravenous (iv) infection with Listeria monocytogenes (L. monocytogenes) accelerated elimination of viable bacteria in the spleen in the early stage of infection (from day 1) and protected mice from the lethal infection. It was suggested that the protective effect of NIN was mediated by the activation of nonimmune macrophages playing a principle role in resistance in the early stage of infection. Two days after ip injection with NIN just before infection, significantly increment in the number of monocytes in the peripheral blood was observed, though macrophage number in the spleen and their intracellular killing activity were unchanged. At 12 hours after infection with L. monocytogenes, a significantly enhanced increase of splenic macrophage number was observed in NIN-treated mice, compared to controls. After ip injection of NIN, interleukin-1 (IL-1), IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) became detectable in the serum or peritoneal cavity. These results suggested that NIN stimulated macrophage-precursor cells in the bone marrow via the production of IL-1, IL-6, GM-CSF by macrophages, accelerated the supply of peripheral macrophages, and such macrophages accumulated into the site of infection in the very early stage of infection. Similar protective effects of NIN were observed by oral administration for 7 days till 1 day before iv infection with L. monocytogenes.
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PMID:Augmentation of host resistance to Listeria monocytogenes infection by a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: ninjin-youei-to). 159 54

The plant-phenol 4-hydroxy-3-methoxyacetophenone (trivial name apocynin) is a strong inhibitor of neutrophil superoxide anion (O2-) release in vitro. In vitro the inhibitory effect of apocynin is restricted to cells with the capacity to release peroxidase and reactive oxygen species (ROS). Peroxidase deficient cells are insensitive to apocynin. In the present study the antiinflammatory activity of apocynin was tested in collagen-induced arthritis in rats. Collagen-immunized rats were treated with different doses of apocynin in the drinking water starting at the onset of joint-swelling and terminating 14 days later, at the time when joint swelling in the control group was maximal. Apocynin-treated animals had a normal plasma level of collagen-specific antibodies, but showed a significant reduction of the joint swelling. Also the plasma IL-6 level in apocynin-treated animals was substantially lower than in control animals. No flare-up of joint swelling after termination of the treatment was observed in the apocynin-treated groups.
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PMID:Antiarthritic activity of the newly developed neutrophil oxidative burst antagonist apocynin. 217 98

Hemorrhage induces a severe suppression of the immune system resulting in increased susceptibility to sepsis. Although studies indicate beneficial effects of calcium channel blockers on cell and organ functions after low-flow conditions, it remains unknown whether such agents have any effects on different immune responses after hemorrhage. To study this, C3H/HeN mice were bled to a mean blood pressure of 35 mm Hg and were maintained for 60 minutes, followed by resuscitation with their own shed blood and adequate fluid. The mice received either the water-soluble calcium channel blocker diltiazem (400 or 2400 micrograms/kg body weight) or saline solution (vehicle). Peritoneal macrophages were obtained by lavage 24 hours later. Antigen presentation was measured by coculturing peritoneal macrophages with the D10.G4.1 helper T-lymphocyte clone. Immune associated antigen (Ia) expression was determined by direct immunofluorescence. Interleukin (IL)-1, 6, and tumor necrosis factor-alpha (TNF) levels in peritoneal macrophage supernatants were measured by use of cytokine-specific cellular assays. Hemorrhage caused a significant decrease in peritoneal macrophage antigen presentation function, Ia expression, and IL-1 and IL-6 synthesis in the vehicle-treated group, whereas TNF levels were increased. However, both doses of diltiazem significantly improved peritoneal macrophage antigen presentation, Ia expression, and IL-1 synthesis. IL-6 synthesis was only increased with high doses of diltiazem, whereas both diltiazem doses decreased TNF production. These results indicate that the calcium channel blocker diltiazem can markedly improve macrophage functions after hemorrhage. The use of diltiazem might offer a new therapeutic modality in the treatment of immunosuppression and in decreasing the susceptibility to sepsis after hemorrhagic shock.
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PMID:Immunoprotective effect of a calcium channel blocker on macrophage antigen presentation function, major histocompatability class II antigen expression, and interleukin-1 synthesis after hemorrhage. 238 17

Infection-induced malnutrition, the most common form of cytokine-induced malnutrition, results from the actions of proinflammatory cytokines, ie, tumor necrosis factor (TNF) and interleukins 1,6, and 8 (IL-1, IL-6, and IL-8). During acute generalized infections, these cytokines initiate the acute-phase reaction. This reaction is quite stereotyped, and includes fever, malaise, myalgia, headaches, cellular hypermetabolism, and multiple endocrine and enzyme responses. In addition, there is heightened catabolism of muscle proteins and many amino acids; flux of free amino acids into the liver; hepatic synthesis of acute-phase plasma proteins; sequestration of iron and zinc; gluconeo-genesis; insulin resistance; impaired cellular uptake of fatty acids from plasma triglycerides; sizable losses of body nitrogen, potassium, magnesium, phosphate, and zinc; retention of body salt and water; heightened metabolic degradation and/or loss of vitamins; and an activation of the immune system. The pathogenesis of cytokine-induced malnutrition is thus vastly different from the malnutrition caused by uncomplicated starvation. Cytokine-induced malnutrition can have a devastating effect on the immune system and its functions. Although proinflammatory cytokines are found in mucosal fluids, where they contribute to the pathogenesis of inflammatory bowel diseases, it is not known whether cytokines play a role in toxigenic, secretory diarrheas such as cholera, which cause huge losses of body water, electrolytes, and bicarbonate while exhibiting no systemic manifestations of an acute-phase reaction.
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PMID:Herman Award Lecture, 1995: infection-induced malnutrition--from cholera to cytokines. 757 15

Hepatic zinc uptake and accumulation were compared in freshly isolated and cultured hepatocytes prepared from control (MT+/+) and metallothionein (MT)-null (MT-/-) mice. In freshly isolated hepatocytes, rapid (10-15 min) exchange of 65Zn was proportional to the Zn concentration in the medium and occurred to the same extent in hepatocytes from MT+/+ and MT-/- mice. In 24 h culture experiments with MT+/+ and MT-/- hepatocytes it was shown that approx. 40% of newly acquired cell-associated Zn was attached to the cell surface and not internalized. In MT+/+ and MT-/- hepatocyte cultures, internalized Zn (intZn) increased in proportion to extracellular Zn. Zn accumulation in MT-/- hepatocytes was only 60% that of MT+/+ cells. Addition of 1 microM dexamethasone (Dex) and recombinant mouse interleukin-6 (IL-6; 100 units/ml) increased MT accumulation by 8.6-fold in MT+/+ hepatocytes (at 50 microM Zn) and there was an associated parallel increase in intZn. Dex and IL-6 did not increase intZn in the MT-/- hepatocytes. At 16 h after an intraperitoneal injection of 5 micrograms/g Zn, plasma and urine Zn concentrations were 69 +/- 10 microM and 86 +/- 25 microM respectively in MT-/- mice (n = 10) and 27 +/- 1 microM and 23 +/- 4 microM respectively in MT+/+ controls (n = 9) (P < 0.001, plasma; P < 0.05, urine). Hepatic cytosolic Zn concentrations doubled in MT+/+ mice and increased by a significant 15% in MT-/- mice. There was no increase in hepatic Zn (dry wt.) concentrations or in total hepatic Zn, demonstrating that the increase in cytosolic Zn in MT-/- mice was due to hepatic water loss rather than net Zn uptake. It appears that even at extreme plasma concentrations of Zn, little if any accumulates within the liver when there is no MT available for its sequestration. That this is not fully demonstrated in vitro is probably due to nature of cell culture, where organ architecture is lost and the external protein binding milieu is less complex.
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PMID:Hepatic zinc in metallothionein-null mice following zinc challenge: in vivo and in vitro studies. 761 65

A number of the members of the family of cytokines including IL-1, IL-2, IL-6, and IL-11 act directly in the brain to induce a febrile response in the rat and other species. The purpose of this study was to examine the effect of interleukin-9 (IL-9) when this cytokine is applied directly to the thermosensitive and pyrogen reactive region of the anterior hypothalamic, preoptic area (AH/POA). In male Sprague-Dawley rats, guide cannulae for microinjection into the AH/POA were implanted stereotaxically, and radio transmitters for monitoring body temperature (Tb) were placed intraperitoneally. Following postoperative recovery, recombinant murine macrophage inflammatory protein (MIP)-1 beta was microinjected in the AH/POA of each rat in a dose of 28 pg/microliters to identify pyrogen reactive sites in the AH/POA. Then recombinant human IL-9 was suspended in pyrogen-free CSF vehicle and microinjected in the same sites in concentrations of 2.4, 24, and 240 U/microliters. In contrast to the pyrexic action of MIP-1 beta, IL-9 failed to elicit a significant alteration in the Tb of the rats at any of the doses tested. IL-9 was also without effect on the intakes of either water or food. These results demonstrate that IL-9 applied to the region of the diencephalon in which other cytokines act to evoke fever may not play a direct role in the thermogenic component underlying the acute phase response. However, as demonstrated in several different cell systems, IL-9 may require a cofactor related to pyrogen for a febrile response to develop.
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PMID:Cytokines and thermoregulation: interleukin-9 injected in preoptic area fails to evoke fever in rats. 789 96

The cytokines interleukin-1 (IL-1) and IL-6 are thought to be important mediators in the suppression of thyroid function during nonthyroidal illness. In this study we compared the effects of IL-1 and IL-6 infusion on the hypothalamus-pituitary-thyroid axis in rats. Cytokines were administered by continuous ip infusion of 4 micrograms IL-1 alpha/day for 1, 2, or 7 days or of 15 micrograms IL-6/day for 7 days. Body weight and temperature, food and water intake, and plasma TSH, T4, free T4 (FT4), T3, and corticosterone levels were measured daily, and hypothalamic pro-TRH messenger RNA (mRNA) and hypophysial TSH beta mRNA were determined after termination of the experiments. Compared with saline-treated controls, infusion of IL-1, but not of IL-6, produced a transient decrease in food and water intake, a transient increase in body temperature, and a prolonged decrease in body weight. Both cytokines caused transient decreases in plasma TSH and T4, which were greater and more prolonged with IL-1 than with IL-6, whereas they effected similar transient increases in the plasma FT4 fraction. Infusion with IL-1, but not IL-6, also induced transient decreases in plasma FT4 and T3 and a transient increase in plasma corticosterone. Hypothalamic pro-TRH mRNA was significantly decreased (-73%) after 7 days, but not after 1 or 2 days, of IL-1 infusion and was unaffected by IL-6 infusion. Hypophysial TSH beta mRNA was significantly decreased after 2 (-62%) and 7 (-62%) days, but not after 1 day, of IL-1 infusion and was unaffected by IL-6 infusion. These results are in agreement with previous findings that IL-1, more so than IL-6, directly inhibits thyroid hormone production. They also indicate that IL-1 and IL-6 both decrease plasma T4 binding. Furthermore, both cytokines induce an acute and dramatic decrease in plasma TSH before (IL-1) or even without (IL-6) a decrease in hypothalamic pro-TRH mRNA or hypophysial TSH beta mRNA, suggesting that the acute decrease in TSH secretion is not caused by decreased pro-TRH and TSH beta gene expression. The TSH-suppressive effect of IL-6, either administered as such or induced by IL-1 infusion, may be due to a direct effect on the thyrotroph, whereas additional effects of IL-1 may involve changes in the hypothalamic release of somatostatin or TRH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Different effects of continuous infusion of interleukin-1 and interleukin-6 on the hypothalamic-hypophysial-thyroid axis. 792 94

Interleukin (IL)-7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma-bearing mice. Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL-7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 +/- 0.2 degrees C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, granulocyte colony stimulating factor (G-CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL-7 in combination with LH. Survival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL-7 plus LH. Increases in levels of IL-1 alpha, IL-6, tumor necrosis factor (TNF alpha) and interferon (IFN gamma) were associated with an increase in the survival of tumor-bearing mice treated with IL-7 and/or LH. These results suggest that changes in T-cell, NK cell and cytokines such as IL-1 alpha, IL-6, TNF-alpha and IFN-gamma in response to IL7 and/or LH might account for prolonged survival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.
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PMID:Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells. 824 52

Does a relatively low concentration of endotoxin in dialysate, seen in our clinical dialysis, enhance cytokine production of monocytes across high-flux membranes? Several investigators using extremely high concentrations of endotoxin in dialysate maintain that it does. In vitro experiments in this study were conducted to clarify this. Peripheral blood monocytes were isolated from healthy volunteers and incubated for 20 hours. The incubation medium was made of back-filtrates obtained either from Pseudomonas-contaminated water with endotoxin concentration of 621 pg/ml or water with 10 ng/ml or 1 microgram/ml of lipopolysaccharide (LPS), by passing it through a high-flux membrane dialyzer. Endotoxin free water and addition of LPS (0.01 to 10 ng/ml) were used as a negative and positive control. Interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor alpha (TNF alpha) were measured. Back-filtrate from Pseudomonas-contaminated water did not enhance cytokine production, while 50 pg/ml of endotoxin in culture medium induced a significant cytokine production. Back-filtrate of 1 microgram/ml of endotoxin solution marginally increased IL-6 production, but not the other two cytokines. However, none of the cytokines was induced by the back-filtrate of 10 ng/ml of endotoxin. Monocytes isolated from blood following three hour extracorporeal recirculation did not alter the production of cytokines. These results cannot confirm the transfer of cytokine inducing substances across the membrane at a relatively low endotoxin concentration in dialysate. Further study should be made as to the minimal requirement of dialysate purification for preventing monocyte stimulation.
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PMID:Do cytokine-inducing substances penetrate through dialysis membranes and stimulate monocytes? 832 Sep 22


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