New rationale for glucocorticoid treatment in septic shock

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Two recent small randomized trials evaluating a 5- to 12-day course of low dose hydrocortisone in patients with septic shock have reported a significant clinical improvement and a reduction in mortality. Recent studies indicate that an overaggressive and unregulated systemic inflammatory response is a major determinant of outcome in sepsis. In septic shock, nonsurvivors as opposed to survivors have over time: (1) significantly higher NF-kB activity in peripheral mononuclear cells, (2) persistent elevation in circulating inflammatory cytokine levels, and (3) elevated ACTH and cortisol levels. Current research recognizes that cytokines can cause a concentration- dependent resistance to endogenous glucocorticoids (GC). It is postulated that an excess of cytokine-induced transcription factors, such as NF-kB, may form complexes with activated glucocorticoid receptors (GCR), preventing GCR interaction with DNA. When T cells are incubated with a combination of cytokines, GC resistance is induced in a cytokine concentration-dependent fashion and reversed by removal of cytokines. Prolonged treatment with physiological doses of exogenous GCs may be necessary to compensate adequately for the inability of target organs to respond to endogenous cortisol and for the inability of the host to produce appropriately elevated levels of GCs. This hypothesis is supported by the laboratory findings of a recent randomized study of patients with unresolving acute respiratory disease.

Original languageEnglish (US)
Pages (from-to)541-550
Number of pages10
JournalJournal of Chemotherapy
Volume11
Issue number6
DOIs
StatePublished - Jan 1 1999

Fingerprint

Septic Shock
Glucocorticoids
Cytokines
Hydrocortisone
NF-kappa B
Glucocorticoid Receptors
Therapeutics
Acute Disease
Adrenocorticotropic Hormone
Survivors
Sepsis
Transcription Factors
T-Lymphocytes
Mortality
DNA
Research

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

New rationale for glucocorticoid treatment in septic shock. / Meduri, Gianfranco.

In: Journal of Chemotherapy, Vol. 11, No. 6, 01.01.1999, p. 541-550.

Research output: Contribution to journalArticle

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