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)

The consequences of glucocorticoid receptor (GR) dysfunction for neuroimmunoendocrine responses to an inflammatory challenge were studied in transgenic mice expressing antisense RNA directed against the GR [GR-impaired (GR-i) mice]. Mice were implanted intraperitoneally with a biotelemetry transmitter to monitor body temperature and locomotion. GR-i mice showed decreased locomotion and body temperature during the dark phase of the diurnal cycle. Intraperitoneal administration of saline caused a rapid increase in body temperature in control mice, which was terminated within 90 min. In GR-i mice, however, body temperature remained elevated for about 6 h. Intraperitoneal injection of endotoxin (10 micrograms/mouse) produced a biphasic fever in control mice. However, in endotoxin-injected GR-i mice, body temperature was not significantly different from their saline-injected controls during the first 6 h. Body temperature then increased and remained elevated during the night period. Both strains showed hypolocomotion after endotoxin. In a second experiment, mice were injected intraperitoneally with saline or endotoxin and killed after 1, 3, 6 or 24 h. In GR-i mice, endotoxin caused an augmented rise in plasma ACTH, but not in corticosterone levels. The endotoxin-induced increase in serum levels of interleukin-1 beta and interleukin-6 was not different between the strains. However, whereas in control mice tumour necrosis factor-alpha levels were below detection at the time points studied, substantial levels of this cytokine were found in the serum of GR-i mice 1 h after endotoxin administration. It may be concluded that life-long impairment of GR evolves in aberrant physiological and humoral responses to an acute inflammatory challenge. These findings expand our understanding about the neuroendocrine and physiological disturbances associated with stress-related disorders.
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PMID:Impaired glucocorticoid receptor function evolves in aberrant physiological responses to bacterial endotoxin. 998 22

Infectious peritonitis results from bacterial contamination of the abdominal cavity. Conventional antibiotic treatment is complicated both by the emergence of antibiotic-resistant bacteria and by increased patient populations intrinsically at risk for nosocomial infections. To complement antibiotic therapies, the efficacy of direct, locally applied pooled human immunoglobulin G (IgG) was assessed in a murine model (strains CF-1, CD-1, and CFW) of peritonitis caused by intraperitoneal inoculations of 10(6) or 10(7) CFU of Pseudomonas aeruginosa (strains IFO-3455, M-2, and MSRI-7072). Various doses of IgG (0.005 to 10 mg/mouse) administered intraperitoneally simultaneously with local bacterial challenge significantly increased survival in a dose-dependent manner. Local intraperitoneal application of 10 mg of IgG increased animal survival independent of either the P. aeruginosa or the murine strains used. A local dose of 10 mg of IgG administered up to 6 h prophylactically or at the time of bacterial challenge resulted in 100% survival. Therapeutic 10-mg IgG treatment given up to 12 h postinfection also significantly increased survival. Human IgG administered to the mouse peritoneal cavity was rapidly detected systemically in serum. Additionally, administered IgG in peritoneal lavage fluid samples actively opsonized and decreased the bacterial burden via phagocytosis at 2 and 4 h post-bacterial challenge. Tissue microbial quantification studies showed that 1.0 mg of locally applied IgG significantly reduced the bacterial burden in the liver, peritoneal cavity, and blood and correlated with reduced levels of interleukin-6 in serum.
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PMID:Efficacy of locally delivered polyclonal immunoglobulin against Pseudomonas aeruginosa peritonitis in a murine model. 1039 Feb 11

1. Accumulating evidence suggests that plasma levels of interleukin-6 (IL-6), a major cytokine stimulating the synthesis of acute phase proteins, are intimately regulated by the central nervous system (CNS). 2. In the present study, effects of intracerebroventricular (i.c. v) injection of N(G)-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole, nitric oxide synthase (NOS) inhibitors, on plasma IL-6 levels and peripheral IL-6 mRNA expression were examined in mice. 3. L-NAME (0.1 - 2 microg per mouse i.c.v.) and 7-nitroindazole (0.2 - 2 microg per mouse i.c.v.) induced a dose-dependent increase in plasma IL-6 levels and a subsequent increase in circulating serum amyloid A, a liver acute-phase protein. In contrast, an intraperitoneal (i.p.) injection of L-NAME up to the dose of 25 microg per mouse had no effect. 4. Pretreatment with yohimbine (alpha(2)-adrenergic antagonist; 1 mg kg(-1) i.p.), or ICI-118,551 (beta(2)-adrenergic antagonist; 2 mg kg(-1) i.p.), but not with prazosin (alpha(1)-adrenergic antagonist; 1 mg kg(-1) i.p.), nor betaxolol (beta(1)-adrenergic antagonist; 2 mg kg(-1) i.p.), significantly inhibited the central L-NAME-induced plasma IL-6 levels. 5. I.c.v. (50 microg per mouse) or i.p. (100 mg kg(-1)) pretreatment with 6-hydroxydopamine had no effect on central L-NAME-induced plasma IL-6 levels. However, intrathecal (i.t.) pretreatment with 6-hydroxydopamine (20 microg per mouse) markedly inhibited central L-NAME-induced plasma IL-6 levels. Both yohimbine (1.5 microg per mouse i.t.) and ICI-118,551 (1.5 microg per mouse i. t.) were effective in inhibition of central L-NAME-induced plasma IL-6 levels. 6. There was an elevation of base-line plasma IL-6 levels in adrenalectomized animals. The adrenalectomy-enhanced levels were not further increased by central L-NAME. 7. L-NAME (2 microg per mouse i.c.v.) induced an increase in IL-6 mRNA expression in liver, spleen, and lymph node. 8. These results suggest that NOS activity in the brain tonically down-regulates peripheral IL-6 by inhibiting adrenaline release from the adrenal medulla.
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PMID:Central injection of nitric oxide synthase inhibitors increases peripheral interleukin-6 and serum amyloid A: involvement of adrenaline from adrenal medulla. 1078 Sep 96

Interleukin-6 (IL-6) is synthesized and released in response to the cytokine inducer lipopolysaccharide (LPS) and IL-1, and acts as an endogenous pyrogen. Systemic administration of LPS and IL-1 to mice induces signs of sickness, including reduction of social exploration, immobility and body weight loss. To assess the role of IL-6 in the induction of sickness behavior, male IL-6-deficient mice (IL-6 -/-, Balb/cAn genetic background) were used and compared to IL-6 +/+ littermates. The depressing effects of intraperitoneal LPS (2.5 microg/mouse) and IL-1beta (1.0 microg/mouse) on behavior and change in body weight were more marked in IL-6 +/+ than in IL-6 -/- mice. The same difference was observed when mice were injected with LPS (5 ng/mouse) and IL-1beta (1 ng/mouse) into the lateral ventricle of the brain (i.c.v.). These results show that IL-6 released at the periphery and /or in the central nervous system plays a role in the behavioral response to LPS and IL-1.
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PMID:Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice. 1100 36

In Escherichia coli 0157 infections, verotoxins (VT) play a critical role in causing the disease, although other factors such as lipopolysaccharide (LPS) and inflammatory cytokines may affect the progression and course of the disease. The present study examined the roles of VT and LPS in induction of serum cytokines and lethality in mice. LD50 of VT2 (13 ng) was c. 10(4)-fold smaller than that of LPS (400 microg). Although the lethal toxicity of these toxins was examined in several experimental conditions, such as VT2 (5, 10, 20, 40 ng/mouse) alone or in combination with LPS (100 microg/mouse) at various times (-2 days to +2 days), no evidence of synergy was observed. VT2 did not augment LPS-induced tumour necrosis factor-alpha (TNF-alpha) or interleukin-6 production, and conversely suppressed TNF-alpha production when it was injected 2 days before LPS challenge. The data failed to indicate either synergic or additive effects of VT and LPS on cytokine production or lethality in mice. In contrast, antagonistic interactions were clearly observed in cytokine production in certain conditions. The results suggested that these toxins may be co-operatively involvedin the pathology of VT-related diseases, but not through synergic interactions.
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PMID:Effects of interaction between Escherichia coli verotoxin and lipopolysaccharide on cytokine induction and lethality in mice. 1102 87

Interleukin (IL)-2 is a cytokine that influences exploratory behavior and central dopamine activity in rodents, and induces schizophrenic-like behavior and cognitive deficits in humans. We presently report that a single i.p. injection of murine IL-2 (0.05-0.80 microg/mouse) induced significant increases in novelty-induced locomotion and exploration in BALB/c mice. These measures were not significantly altered in mice that were pre-exposed to the test cage prior to cytokine injection. The IL-2-induced behavioral changes were not further augmented by repeated intermittent injections (five daily i.p. injections; 0.4 microg/mouse), however. Nonetheless, during the treatment period, activity scores of IL-2-treated mice significantly exceeded those of mice receiving saline; hence, repeated injections of IL-2 induced a persistent behavioral activation. IL-2 treatment also increased sensitivity to the behavior-stimulating effects of GBR 12909, a highly selective dopamine uptake inhibitor. This effect was a very long-lasting one since the dopamine agonist was administered 6 weeks after cessation of IL-2 treatment. The latter finding indicates that IL-2 interacts with the mesolimbic dopamine system, changing its sensitivity to seemingly different substances. Based on these data, and those of Zalcman and colleagues (S. Zalcman, I. Savina, R.A. Wise, Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats, Brain Res. 847 (1999) 276-283), it is suggested that cytokines can influence the development of behavioral abnormalities that are characteristic of aberrant mesolimbic dopamine activity via sensitization-like processes.
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PMID:Interleukin-2 potentiates novelty- and GBR 12909-induced exploratory activity. 1131 62

Interleukin-6 (IL-6) regulates essential physiological functions such as acute phase reaction, immune response and hematopoiesis. We here studied possible protective effects of IL-6 on skin damage caused by 7,12-dimethylbenz[a]anthracene (DMBA) by using IL-6 null mice. The mice were topically applied with a single dose of DMBA (500 microg /mouse) on the dorsal skin. Osmotic pumps filled with recombinant human IL-6 (rhIL-6) were implanted subcutaneously on the ventral side of the mice. Control mice received PBS instead of rhIL-6 by the pump. Severe skin damage was observed in IL-6-null mice, whereas only epidermal hyperplasia was observed in the wild-type mice. Recombinant hIL-6 treatment to DMBA-treated IL-6-null mice suppressed the occurrence of the skin damage, indicating.
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PMID:Interleukin-6 protects skin lesion caused by 7,12-dimethylbenz[a]anthracene. 1273 34

Glucuronoxylomannan (GXM), the principal constituent of the Cryptococcus neoformans capsule, modulates the inflammatory response of human monocytes in vitro. Here we examine the efficacy of GXM as a novel anti-inflammatory compound for use against experimental septic arthritis. Arthritis was induced in mice by the intravenous injection of 8 x 10(6) CFU of type IV group B streptococcus (GBS). GXM was administered intravenously in different doses (50, 100, or 200 microg/mouse) 1 day before and 1 day after bacterial inoculation. GXM treatment markedly decreased the incidence and severity of articular lesions. Histological findings showed limited periarticular inflammation in the joints of GXM-treated mice, confirming the clinical observations. The amelioration of arthritis was associated with a significant reduction in the local production of interleukin-6 (IL-6), IL-1beta, macrophage inflammatory protein 1alpha (MIP-1alpha), and MIP-2 and an increase in systemic IL-10 levels. Moreover, peritoneal macrophages derived from GXM-treated mice and stimulated in vitro with heat-inactivated GBS showed a similar pattern of cytokine production. The present study provides evidence for the modulation of the inflammatory response by GXM in vivo and suggests a potential therapeutic use for this compound in pathologies involving inflammatory processes.
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PMID:Glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans, inhibits the progression of group B streptococcal arthritis. 1550 66

There is growing evidence that chemokines play important roles in the immune surveillance of central nervous system (CNS). In the CNS, microglia are primary immune effector cells and secrete various chemokines in response to their microenvironment. Using the RT-PCR procedure and indirect immunofluorescence analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat primary microglia without any stimulation, but not in primary astrocytes, although both cell types expressed CCR1 mRNA, which is a receptor for CCL6. Furthermore, immunohistochemical analysis demonstrated that microglia produced CCL6 protein in a normal brain, suggesting that microglia may be the primary source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of microglia and astrocytes in vitro. The CCL6-mediated cell migration was blocked by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot analysis showed that the phosphorylation of Akt could be induced by treating microglia with a recombinant CCL6, suggesting that CCL6 functions by activating the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced the expression of both CCL6 mRNA and protein in microglia, while other proinflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha and an anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS.
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PMID:Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell-cell communication. 1608 46

Gastrointestinal motility disturbances during endotoxemia are probably caused by lipopolysaccharide (LPS)-induced factors: candidates include nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss, and interleukin-6. Flow cytometry was used to determine the effects of LPS and these factors on gastric emptying (evaluated indirectly by determining percent gastric retention; %GR) and gastrointestinal transit (GIT) in male BALB/c mice (23-28 g). NO (300 microg/mouse, N = 8) and TNF-alpha (2 microg/mouse, N = 7) increased (P < 0.01) GR and delayed GIT, mimicking the effect of LPS (50 microg/mouse). During early endotoxemia (1.5 h after LPS), inhibition of inducible NO synthase (iNOS) by a selective inhibitor, 1400 W (150 microg/mouse, N = 11), but not antibody neutralization of TNF-alpha (200 microg/mouse, N = 11), reversed the increase of GR (%GR 78.8 +/- 3.3 vs 47.2 +/- 7.5%) and the delay of GIT (geometric center 3.7 +/- 0.4 vs 5.6 +/- 0.2). During late endotoxemia (8 h after LPS), both iNOS inhibition (N = 9) and TNF-alpha neutralization (N = 9) reversed the increase of GR (%GR 33.7 +/- 2.0 vs 19.1 +/- 2.6% (1400 W) and 20.1 +/- 2.0% (anti-TNF-alpha)), but only TNF-alpha neutralization reversed the delay of GIT (geometric center 3.9 +/- 0.4 vs 5.9 +/- 0.2). These findings suggest that iNOS, but not TNF-alpha, is associated with delayed gastric emptying and GIT during early endotoxemia and that during late endotoxemia, both factors are associated with delayed gastric emptying, but only TNF-alpha is associated with delayed GIT.
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PMID:Inducible nitric oxide synthase and tumor necrosis factor-alpha in delayed gastric emptying and gastrointestinal transit induced by lipopolysaccharide in mice. 1714 55


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