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)

Cachexia frequently occurs in the late stages of cancer, and is difficult to manage. We previously reported that interleukin-6 (IL-6) cDNA transfection into Lewis lung carcinoma (LLC-IL6) induced cachexia-like symptoms in C57BL/6 mice. This was thought to be a useful experimental model of cancer cachexia. We have examined the effects of two eicosanoids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in order to evaluate whether they could relieve cachexia. LLC-IL6-bearing animals were divided into three treatment groups receiving DHA, EPA or water as the control; 80-microliter samples of these compounds (purity > 95%) were administered orally by catheter daily starting 7 days after tumor transplantation. Tumor growth curves were similar in the three groups. There were no differences in water or food intake in the three groups. However, body weight, a marker of cachexia, was significantly higher in treated mice than in the control group. Sixteen days after tumor transplantation, the mean body weight was 17.45 g (P < 0.05), 17.2 g and 16.41 g in the groups receiving DHA, EPA and water respectively. The eicosanoids did not affect serum levels of IL-6. Ubiquitination of muscle protein, a marker of proteolysis coupled to cachexia, was compared in LLC-IL6- and LLC-transplanted mice. The eicosanoids prevented the ubiquitination of approximately 180 kDa protein. These results suggest that eicosanoids may prevent the cachexia mediated by IL-6.
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PMID:Improvement by eicosanoids in cancer cachexia induced by LLC-IL6 transplantation. 895 67

Thermoregulation during exercise was studied in seven women who were taking oral contraceptive pills for 3 weeks of each month. The subjects were studied once in the 3rd week of taking the pill (P) and once during the following week when they took no pil (N). Rectal temperature (Tre), heart rate (fc) and evaporative water loss (EWL, ventilated capsule technique) were measured while they walked on a treadmill for 60 min at 4.8 km.h-1 at a 10% gradient. Ambient temperature was 22 degrees C. A venous blood sample was drawn 30 min before each experiment for measurement of hematocrit (packed cell volume, PCV), plasma osmolality (Osmpl), and plasma levels of the endogenous pyrogens interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). Resting Tre was 0.31 degree C higher in P than in N (P < 0.01) and Tre remained higher in P throughout the entire exercise period (P < 0.01). Threshold Tre for the onset of EWL was 0.32 degree C higher in P than in N (P < 0.01). Exercise fc was 6.5 beats.min-1 higher in P than in N (P < 0.01). There was no significant difference in PCV, Osmpl, IL-1 beta or IL-6 between P and N. It was concluded that the administration of synthetic progestins in oral contraceptives causes an upward shift in the threshold for heat loss responses, resulting in higher body core temperatures both at rest and during exercise. There was no evidence that these alterations in thermoregulation were mediated by changes in body fluid balance or in plasma levels of IL-1 beta or IL-6.
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PMID:Thermoregulation during exercise in women who are taking oral contraceptives. 900 55

The effects of different methylmercury (MeHg) forms on the immune system and the hypothalamic pituitary adrenal (HPA) axis were assessed. The lymphocyte response to Concanavalin A (Con A) stimulation, blood levels of interleukin-6 (IL-6), adrenocorticotrophin hormone (ACTH), and corticosterone in the presence of different MeHg compounds was measured. Rats were exposed to methylmercury sulfide [(MeHg)2S] and methylmercury chloride (MeHgCl) at concentrations of 5 and 500 micrograms per liter in the drinking water for 8 or 16 weeks. Short-term exposure (8 weeks) at both, low- and high-doses of (MeHg)2S significantly enhanced lymphocyte responsiveness. MeHgCl only induced increased lymphocyte responsiveness at the low-dose exposure. Circulating levels of IL-6 after short-term exposure were increased in the MeHgCl-exposed group. The HPA axis activation was demonstrated by increased levels of ACTH and corticosterone levels. This response was predominant in low-dose exposed animals. Long-term (16 weeks) exposure resulted in a reduction in lymphocyte prolife ration after both low- and high-dose MeHgCl exposures. The (MeHg)2S exposure resulted in a 3-fold increase in the proliferative response. Levels of ACTH were elevated 3-fold in the (MeHg)2S-exposed group and no increase of corticosterone was observed in the high-dose exposed group at 8 weeks, no effect of (MeHg)2S was observed at 16 weeks. The MeHgCl exposed group showed an increase in ACTH and corticosterone levels at 8 weeks; this response was not observed at 16 weeks. These data indicate that exposure to MeHg compounds enhances T-cell proliferation in most of the cases, in a dose- and time-dependent fashion. Release of IL-6 also depends on the length of exposure. Early increases in circulating ACTH at 8 weeks also suggest activation of the HPA axis. This may contribute to the production of IL-6 and surveillance of regulatory homeostatic responses against environmental agents that mimic stress-like responses.
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PMID:Neuroimmunological effects of exposure to methylmercury forms in the Sprague-Dawley rats. Activation of the hypothalamic-pituitary-adrenal axis and lymphocyte responsiveness. 909 50

In a continuous one-bottle sucrose intake test, 4-month-old autoimmune MRL-Ipr mice show a shift to the right along the X-axis of the concentration-intake function, compared to congenic MRL +/+ controls. Using a brief (60-min) and a continuous (48-h) two-bottle test, the present report examines potential factors that could account for the reduced responsiveness to a palatable stimulus. Study 1 examines whether preference for sucrose is associated with age, changes in food/water intake, or impaired renal function. Reduced preference for sucrose was observed in 5-6-week-old MRL-Ipr males, although food/water intake or blood creatinine levels did not differ from control values. Immunosuppressive treatment abolished this deficit, suggesting a role of immune factor(s). Study 2 tests the hypothesis that chronic upregulation of the neuroactive cytokine interleukin-6 (IL-6), reported to occur from 3 weeks of age in young MRL-Ipr mice, reduces preference for sucrose. Sustained administration of IL-6 was produced by infecting healthy MRL +/+, C3H.SW and Balb/C mice with adenovirus vector carrying cDNA for murine IL-6. This resulted in high serum IL-6 levels over 5 days, a rapid decline in preference for sucrose and low blood glucose levels. The results from Study 1 indicate that impaired sensitivity to sucrose in MRL-Ipr mice can be detected before autoimmune disease is florid in MRL-Ipr mice. The results from Study 2 are consistent with altered motivation/emotional states after infection, and point to sustained IL-6 production as an early mechanism in behavioral alterations during chronic autoimmune/inflammatory conditions.
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PMID:Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6. 929 5

Studies were performed to investigate the relationship between serum interleukin-6 (IL-6) and the nutritional status in chronic hemodialysis patients. Serum IL-6 in 45 patients (21 men and 24 women), each with chronic renal failure and having undergone hemodialysis for more than 3 years, was measured before and after a dialysis session. The nutritional status of each patient was evaluated by measuring body mass index (BMI), body weight loss for 3 years, midarm muscle area (MAMA), serum albumin, prealbumin, and insulin-like growth factor-1. Serum IL-6 was significantly higher in the patients undergoing hemodialysis (11.7 +/- 2.8 pg/mL) than in healthy volunteers (< 0.6 pg/mL). There was no further increase in serum IL-6 after a dialysis session when the extracellular water volume was corrected by the ultrafiltrate volume. Predialytic serum IL-6 was significantly correlated with serum albumin (r = -0.4, P = 0.006), cholinesterase (r = -0.51, P = 0.001), body weight change for 3 years (r = -0.48, P = 0.001) and MAMA r = -0.39, P = 0.05). With the patients divided into two groups, a high serum IL-6 (>10 pg/mL) group and low serum IL-6 (<10 pg/mL) group, the body weight loss for 3 years (-4.60% +/- 1.39% v 0.76 +/- 0.75%, P < 0.01) was significantly higher, and the serum albumin level (3.66 +/- 0.10 g/dL v 3.96 +/- 0.05 g/dL, P < 0.05) was significantly lower in those patients with high serum IL-6 than in those with low serum IL-6. The results of a multiple regression analysis indicated that the serum IL-6 level was dependent on the duration of hemodialysis, age, and the dialysis membrane properties. These results suggest that the nutritional status in chronic hemodialysis patients was affected, at least in part, by the circulating IL-6 level. Multiple factors, such as long-term hemodialysis, aging, and the use of a regenerated cellulose membrane dialyzer, were associated with this increased level of IL-6.
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PMID:Interleukin-6 may mediate malnutrition in chronic hemodialysis patients. 942 58

In recent years, clinical application of recombinant cytokines has been expected as a novel drug for various diseases. However, cytokines have generally poor stability in vivo, so they required of very high doses to achieve sufficient clinical effect. In addition, because cytokines have pleiotropic functions, they would cause unfavourable side-effects. Therefore an drug delivery system (DDS) is necessary for clinical use, which stabilizes the cytokines and potentiates only the expected function from other unfavorable ones in vivo. Then we performed the chemical modification of cytokines with water-soluble polymers to overcome such problems as poor stability and pleiotropic activities. This approach includes some advantages that decrease renal excretion rate of proteins and prevent the degradation by proteases. This would result in prolonging the half-lives of bioactive proteins and potentiating their clinical effects. Interestingly, we found that the polymer-conjugated cytokines, that we named hybrid-cytokines, for instance, polyethylene glycol-modified interleukin-6 (PEG-IL-6), were able to increase selectively in their function of promoting platelet production, but not in other unfavourable functions. This effects were suggested for a result of the change in the systemic distribution pattern by pegylation of proteins. In this review, we proposed that the DDS using hybrid-cytokines would be able to increase the stability and regulate the spectrum of the functions of the cytokines by controlling the pharmacokinetics and pharmacodynamics in vivo. This will provide a fundamental information enabling us to design the hybrid-proteins applicable to therapeutic use.
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PMID:[Molecular design of polymer-conjugated cytokines and its application for drug delivery systems]. 954 38

This study examined the immunological responses to cold exposure together with the effects of pretreatment with either passive heating or exercise (with and without a thermal clamp). On four separate occasions, seven healthy men [mean age 24.0 +/- 1.9 (SE) yr, peak oxygen consumption = 45.7 +/- 2.0 ml. kg(-1). min(-1)] sat for 2 h in a climatic chamber maintained at 5 degrees C. Before exposure, subjects participated in one of four pretreatment conditions. For the thermoneutral control condition, subjects remained seated for 1 h in a water bath at 35 degrees C. In another pretreatment, subjects were passively heated in a warm (38 degrees C) water bath for 1 h. In two other pretreatments, subjects exercised for 1 h at 55% peak oxygen consumption (once immersed in 18 degrees C water and once in 35 degrees C water). Core temperature rose by 1 degrees C during passive heating and during exercise in 35 degrees C water and remained stable during exercise in 18 degrees C water (thermal clamping). Subsequent cold exposure induced a leukocytosis and granulocytosis, an increase in natural killer cell count and activity, and a rise in circulating levels of interleukin-6. Pretreatment with exercise in 18 degrees C water augmented the leukocyte, granulocyte, and monocyte response. These results indicate that acute cold exposure has immunostimulating effects and that, with thermal clamping, pretreatment with physical exercise can enhance this response. Increases in levels of circulating norepinephrine may account for the changes observed during cold exposure and their modification by changes in initial status.
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PMID:Immune changes in humans during cold exposure: effects of prior heating and exercise. 1044 30

The active entity responsible for inducing interleukin-6 production by human gingival fibroblasts was partially purified by ion-exchange chromatography from the water-soluble fraction of Mycoplasma salivarium cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the final preparation revealed one densely stained band with a molecular weight of 20.6 kilodaltons and two faint bands with molecular weights of 40.5 and 82.5 kilodaltons. The specific activity of the final preparation was 34-fold higher than that of the starting water-soluble fraction. The interleukin-6-inducing activity was destroyed by proteinase K and reduced 70% by lipoprotein lipase and heat treatment, but was not affected by deoxyribonuclease I or endoglucosidase D. The final preparation induced small amounts of tumor necrosis factor-alpha and interleukin-lbeta in a myelomonocytic cell line, THP-1 cells, but did not induce interleukin-6. The ability of Escherichia coli lipopolysaccharide to stimulate human gingival fibroblasts to release interleukin-6 was dependent upon the presence of serum in the assay medium, but that of the final preparation from M. salivarium was not. Thus, we partially purified the protein(s) from M. salivarium which were capable of stimulating human gingival fibroblasts to release interleukin-6 by a mechanism different from that of E. coli lipopolysaccharide.
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PMID:Partial purification and characterization of the active entity responsible for inducing interleukin-6 production by human gingival fibroblasts from Mycoplasma salivarium cells. 1060 9

We have reported previously that axonal degeneration in specific brain regions occurs in rats infected with the parasite Trypanosoma brucei. These degenerative changes occur in spatiotemporal association with over-expression of pro-inflammatory cytokine messenger RNAs in the brain. To test how aspirin-like anti-inflammatory drugs might alter the disease process, we fed trypanosome-infected rats with 200mg/kg of sodium salicylate (the first metabolite of aspirin) daily in their drinking water. Sodium salicylate treatment in uninfected rats did not cause any neural damage. However, sodium salicylate treatment greatly exacerbated neurodegeneration in trypanosome-infected rats, resulting in extensive terminal and neuronal cell body degeneration in the cortex, hippocampus, striatum, thalamus, and anterior olfactory nucleus. The exaggerated neurodegeneration, which occurred in late stages of infection, was temporally and somewhat spatially associated with a late-appearing enhancement of messenger RNA expression of interleukin-1beta, interleukin-1beta converting enzyme, tumor necrosis factor-alpha, and inhibitory factor kappaBalpha in the brain parenchyma. Restricted areas showed elevations in messenger RNA expression of interleukin-1 receptor antagonist, interleukin-6, inducible nitric oxide synthase, interferon-gamma, and inducible cyclooxygenase. The association suggests that increased production of pro-inflammatory cytokines in the brain may be an underlying mechanism for neural damage induced by the chronic sodium salicylate treatment. Furthermore, the results reveal a serious complication in using aspirin-like drugs for the treatment of trypanosome infection.
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PMID:Chronic sodium salicylate treatment exacerbates brain neurodegeneration in rats infected with Trypanosoma brucei. 1068 22

Metallothionein (MT) is a low-molecular-weight, sulfhydryl-rich, metal-binding protein that can protect against the toxicity of cadmium, mercury, and copper. However, the role of MT in arsenic (As)-induced toxicity is less certain. To better define the ability of MT to modify As toxicity, MT-I/II knockout (MT-null) mice and the corresponding wild-type mice (WT) were exposed to arsenite [As(III)] or arsenate [As(V)] either through the drinking water for 48 weeks, or through repeated sc injections (5 days/week) for 15 weeks. Chronic As exposure increased tissue MT concentrations (2-5-fold) in the WT but not in MT-null mice. Arsenic by both routes produced damage to the liver (fatty infiltration, inflammation, and focal necrosis) and kidney (tubular cell vacuolization, inflammatory cell infiltration, and interstitial fibrosis) in both MT-null and WT mice. However, in MT-null mice, the pathological lesions were more frequent and severe when compared to WT mice. This was confirmed biochemically, in that, at the higher oral doses of As, blood urea nitrogen (BUN) levels were increased more in MT-null mice (60%) than in WT mice (30%). Chronic As exposures produced 2-10 fold elevation of serum interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha levels, with greater increases seen by repeated injections than by oral exposure, and again, MT-null mice had higher serum cytokines than WT mice after As exposure. Repeated As injections also decreased hepatic glutathione (GSH) by 35%, but GSH-peroxidase and GSH-reductase were minimally affected. MT-null mice were more sensitive than WT mice to the effect of GSH depletion by As(V). Hepatic caspase-3 activity was increased (2-3-fold) in both WT and MT-null mice, indicative of apoptotic cell death. In summary, chronic inorganic As exposure produced injuries to multiple organs, and MT-null mice are generally more susceptible than WT mice to As-induced toxicity regardless of route of exposure, suggesting that MT could be a cellular factor in protecting against chronic As toxicity.
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PMID:Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals. 1082 79


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