The Cytokines: Physiological and Pathophysiological Aspects

Evans, Stuart; Whicher, J T

doi:10.1016/s0065-2423(08)60194-8

Cited by 13 publications

(7 citation statements)

References 502 publications

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“…IL-10 is inhibitory for cytokine synthesis (reviewed in ref. 18), and this is presumably the reason why it is protective. Therefore, if CsA caused harm by inhibiting the synthesis of IL-10, the reason for this harm is not readily apparent from our data.…”

Section: Discussionmentioning

confidence: 99%

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Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

et al. 2001

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Cyclosporin A (CsA), an inhibitor of T cell cytokine production, protects mice against staphylococcal enterotoxin B (SEB) intoxication. To determine whether CsA treatment would work in a species closer to humans. 4 rhesus monkeys were given 50 mg/kg CsA followed by an intratracheal challenge with approximately 6 LD50 of SEB. The CsA was not protective: one of the monkeys died and the other three had to be euthanised when they became moribund. All monkeys made IL-2, TNF, and IFN-gamma in response to SEB. In addition, there was about a 10-fold increase in ACTH levels 2 hr after SEB challenge. CsA significantly suppressed in vitro proliferation of lymphocytes from treated monkeys. Both CsA-treated monkeys and monkeys that had been challenged in a previous experiment with a lethal dose of SEB but had received no cyclosporin had pathologic changes in several organs. The most prominent changes were marked edema and leukocytic infiltration of the bronchial and bronchiolar mucosa. The CsA treatment appeared to reduce the intensity of lung inflammation, but this effect was not sufficient to protect the monkeys. The results suggest that CsA alone may not be an effective therapeutic agent for humans suffering from SEB intoxication or gram-positive septic shock.

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Section: Discussionmentioning

confidence: 99%

“…A considerable body of evidence implicates TNF as a major mediator in the pathogenesis of gram positive and gram negative bacterial sepsis and endotoxic shock (reviewed in ref. 18). TNF is produced by human cells in vitro in response to SEB (33,61).…”

Section: Discussionmentioning

confidence: 99%

Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

et al. 2001

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“…These effects required acute elevations of IL-6 in the circulation to levels higher than 25-65 pg/ml, which were consistently achieved only with the 3.0-and 10.0-pg/kg IL-6 doses. Interestingly, such levels fall within the range of plasma IL-6 concentrations associated with common inflammatory and infectious pro cesses [17][18][19][20][21][22], suggesting that IL-6 may be a principal ac tivator of the stress system in these conditions.…”

Section: Discussionmentioning

confidence: 99%

Dose Effects of Recombinant Human lnterleukin-6 on Pituitary Hormone Secretion and Energy Expenditure

et al. 1997

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Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL·6 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 µg/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-µg/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-µg/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 µg/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 µg/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermogenesis.

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“…A relationship exists between the route of infection and HCV genotype: 1b genotype is more often associated with hemotransfusions, medical manipulations, and occupational infection; 3a genotype is associated with intravenous drug use; and 2a genotype is more often diagnosed in co-infection with HBV [13]. Attempts at detecting the relationship between HCV genotype and morphological activity or severity of fibrosis in CVHC patients failed, though retrospective studies aimed at detection of HCV genotypes in patients with liver cirrhosis and hepatocellular carcinoma clearly demonstrated the highest incidence of 1b genotype [14].…”

Section: Resultsmentioning

confidence: 99%

“…Soluble receptors can also function as competitive antagonists. They act as cytokine transmitters protecting these agents from protease destruction and prolonging their life span in systemic circulation, and participate in cytokine transport to the focus of injury and their elimination from the body [1,10,13]. The causes of increased concentrations of soluble cytokine receptors in biological fluids are now discussed.…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Changes in TNF-α Production by Blood Mononuclears in Chronic Viral Hepatitis C

et al. 2005

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Chronic viral hepatitis C is associated with decreased production of TNF-alpha by the peripheral blood mononuclear leukocytes irrespective of virus genotype and degree of the morphological activity of the process in the liver. This process positively correlates with the increase in the content of TNF-alpha soluble receptor (molecular weight 55 kDa), which can play a role in the mechanisms of immunopathogenesis of long persistence of hepatitis C virus in the body.

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The Cytokines: Physiological and Pathophysiological Aspects

Cited by 13 publications

References 502 publications

Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

Cellular and Cytokine Responses in the Circulation and Tissue Reactions in the Lung of Rhesus Monkeys (Macaca mulatta) Pretreated with Cyclosporin A and Challenged with Staphylococcal Enterotoxin B

Dose Effects of Recombinant Human lnterleukin-6 on Pituitary Hormone Secretion and Energy Expenditure

Molecular Mechanisms of Changes in TNF-α Production by Blood Mononuclears in Chronic Viral Hepatitis C

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