Increased survival with methylprednisolone treatment in canine endotoxin shock

White, Gary L.; Archer, L. T.; Beller, B. K.; Hinshaw, Lerner B.

doi:10.1016/0022-4804(78)90131-2

Cited by 46 publications

(15 citation statements)

References 17 publications

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“…In contrast to the modest doses of these agents used in replacement therapy and in the treatment of chronic immune disorders, very high-dose (30 mg/kg i.v.) corticosteroid therapx has recently been reported to be of benefit in the tre oment of endotoxic shock and the adult respiratory distress syndrome (12)(13)(14)(15)(16). It seems likely that the effects of these agents at very high doses might be different from those observed at low doses; in fact, several mechanisms for antiinflammatory action of corticosteroids have been reported, and the concentration ranges at which they are effective differ.…”

Section: Discussionmentioning

confidence: 99%

“…They include hemodialysis neutropenia and pulmonary dysfunction (1,4,5), the vasculitis of cholesterol embolization syndrome (6), and the adult respiratory distress syndrome (7)(8)(9). Corticosteroids have been shown to blunt the PMN responses to activated complement components (10), and the recent finding that high-dose corticosteroids inhibit granulocyte aggregation in vitro and in vivo (7,11) suggested a possible mechanism for their reported efficacy in the adult respiratory distress syndrome and endotoxic shock (12)(13)(14)(15)(16)(17)(18). High-dose cortico1Abbreviations used in this paper: DEX, dexamethasone sodium phosphate; FMLP, N-formyl-methionine-leucinephenylalanine; HBSS, Hanks' balanced salt solution; HC, hydrocortisone sodium succinate; MP, methylprednisolone sodium succinate; PBS, phosphate-buffered saline; PMN, granulocyte. steroid therapy has also recently been tried in other diseases such as idiopathic rapidly progressive glomerulonephritis, and further trials are being contemplated (6,19).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Skubitz¹,

Craddock²,

Hammerschmidt³

et al. 1981

J. Clin. Invest.

116

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A B S T R A C T Inhibition of complement-mediated granulocyte aggregation has recently been proposed as a mechanism of action of high-dose corticosteroids in shock states. Postulating that such inhibition might be effected through alteration of receptor function, we examined the effect of methylprednisolone (MP), hydrocortisone (HC), and dexamethasone (DEX) on the extent and kinetics of binding of the synthetic chemotaxin f-methionine-leucine-phenylalanine (FMLP) to its specific receptor on the granulocyte surface. Dose

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Skubitz¹,

Craddock²,

Hammerschmidt³

et al. 1981

J. Clin. Invest.

116

View full text Add to dashboard Cite

show abstract

“…Both direct and indirect insults to the alveolar-capillary membrane have been used in various animal species to model ARDS (33). Several studies using animal models of sepsis and lung injury have shown that corticosteroids decrease morbidity and mortality if given simultaneously with or before the experimental insult (21,34). Pretreatment with corticosteroids was also shown to increase the survival rate in acute lung injury induced by aspiration pneumonitis and oleic acid-induced pulmonary edema (35,36).…”

Section: Animal Researchmentioning

confidence: 99%

Corticosteroids in acute respiratory distress syndrome

Fernandes

Zin

Rocco

2005

Braz J Med Biol Res

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Improving the course and outcome of patients with acute respiratory distress syndrome presents a challenge. By understanding the immune status of a patient, physicians can consider manipulating proinflammatory systems more rationally. In this context, corticosteroids could be a therapeutic tool in the armamentarium against acute respiratory distress syndrome. Corticosteroid therapy has been studied in three situations: prevention in high-risk patients, early treatment with high-dose, short-course therapy, and prolonged therapy in unresolving cases. There are differences between the corticosteroid trials of the past and recent trials: today, treatment starts 2-10 days after disease onset in patients that failed to improve; in the past, the corticosteroid doses employed were 5-140 times higher than those used now. Additionally, in the past treatment consisted of administering one to four doses every 6 h (methylprednisolone, 30 mg/kg) versus prolonging treatment as long as necessary in the new trials (2 mg kg -1 day -1 every 6 h). The variable response to corticosteroid treatment could be attributed to the heterogeneous biochemical and molecular mechanisms activated in response to different initial insults. Numerous factors need to be taken into account when corticosteroids are used to treat acute respiratory distress syndrome: the specificity of inhibition, the duration and degree of inhibition, and the timing of inhibition. The major continuing problem is when to administer corticosteroids and how to monitor their use. The inflammatory mechanisms are continuous and cyclic, sometimes causing deterioration or improvement of lung function. This article reviews the mechanisms of action of corticosteroids and the results of experimental and clinical studies regarding the use of corticosteroids in acute respiratory distress syndrome.

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“…As emphasized previously (lo), it is crucial to demonstrate that the challenge inoculum of gram-negative bacteria does not contain a lethal quantity of preformed endotoxin. Adrenal corticosteroids, if given early and in pharmacologic doses, protect against endotoxemic mortality (13)(14)(15)(16)(17)(18). Therefore, if gram-negative bacteria are inoculated in numbers sufficient to cause death from both preformed endotoxin as well as from infection, then adrenal corticosteroids alone or antibiotics alone, even if given promptly, could not be expected to prevent mortality whereas their combination, each protective against the respective lethal factors, would be protective.…”

mentioning

confidence: 97%

Experimental Gram-Negative Bacterial Sepsis: Optimal Methylprednisolone Requirements for Prevention of Mortality Not Preventable by Antibiotics Alone

Greisman

1982

Experimental Biology and Medicine

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Outbed ICR mice were inoculated ip with one LD,-,, Escherichia coli 0:18, Proteus mirabilis, or Klebsiella pneumoniae. After carefully timed intervals, aminoglycoside antibiotics were begun at dosages and intervals predetermined to constitute optimal therapy. With progressive delay of antibiotic therapy, mortality rates increased progressively from 0 to 90-1W0. Standardized models of infection were obtained by selecting delay periods before initiating antibiotic therapy such that 50 to 70% mortality rates resulted.In these models, 30 mg/kg methylprednisolone (MP) given prior to or concomitantly with the delayed antibiotic therapy and repeated 4 hr later was previously shown capable of preventing gram-negative septic mortality not preventable by the optimal antibiotic therapy alone.The present studies quantitate the optimal quantities of MP required for such protection. It was found that (1) in the absence of aminoglycoside antibiotics, MP consistently failed to reduce mortality; (2) in the antibiotic-treated animals, a single im injection of 30 mg/kg MP provided definite protection. A second and a third injection of 30 mdkg of MP at 4-hr intervals provided additional, but decremental, increments of protection; (3) decreasing the dose of MP to 10 mg/kg or less consistently reduced its protective activity; (4) increasing the dose of MP to 60 mg/kg or greater consistently reduced its protective activity; (5) short additional increments in delay in initiating antibiotic and MP therapy annulled the protective activity of MP. The findings indicate that the ability of MP to reduce murine mortality from gram-negative bacterial sepsis is not only critically restricted by the requirements for its early administration in conjunction with appropriate antibiotics, but also by its relatively narrow optimal dose-response range and the decremental increments in its effectiveness upon repetitive administration. 436

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Increased survival with methylprednisolone treatment in canine endotoxin shock

Cited by 46 publications

References 17 publications

Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocyte aggregates in vitro.

Corticosteroids in acute respiratory distress syndrome

Experimental Gram-Negative Bacterial Sepsis: Optimal Methylprednisolone Requirements for Prevention of Mortality Not Preventable by Antibiotics Alone

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