# STEROID ACTION IN BACTERIAL ENDOTOXIC SHOCK

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 1988 · $122,724

## Abstract

Our hypothesis is that bacterial endotoxin evokes the release of
mediators from the reticuloendothelial system that mediate
alterations in hormone regulated metabolism in the liver.
Evidence obtained in our laboratory during the first 21/2 years of
this project suggest immunomodulatory monokines, released
following endotoxin administration interact with glucocorticoid
actionon gene expression.  In the continuation of this study we
propose to characterize the role of monokines, such as IL 1, TNF,
and IFN, in altered glucocorticoid action during endotoxemia.
This will be done by titrating the inhibitory activity of mediator-
rich plasma (obtained from CF-1 mice infected with BCG and
challenged with 2 micrograms of bacterial endotoxin) in C3H/HeJ
mice and Reuber H35 rat hepatoma cell (RHC) cultures.  Altered
glucocorticoid induction of tryptophan oxygenase (TO), tyrosine
aminotransferase (TAT), phosphoenolpyruvate carboxykinase
(PEPCK), and glyogen synthase (GS) will be monitored after
monokine treatment.  Impaired induction of these liver enzymes
will be correlated with decreased hepatic cytosolic binding of
dexamethasone.  In addition we will titrate the inhibitory activity
of factors released from endotoxin treated Kupffer cells.  Cross-
adsorption of mediator-rich plasma and Kupffer cell fluids with
monospecific antibodies to known monokines will assess the
possible synergistic or antagonistic effects of monokines on
altered glucocorticoid action.  In the proposed study we will also
assess the influence of glucocorticoids on the monokine mediators
that are found to affect glucocorticoid action during endotoxic
shock.  We will measure the inhibition of induction of TO, TAT,
PEPCK and GS in adrenal-ectomized (adrx) mice and adrx mice
reconstituted with exogenous steroid.  Recombinant IL 1, TNF and
IFN will be used in both mice and RHC to test the influence of
steroids on monokine action.  The long term goal of this proposed
research is to understand the molecular events underlying
glucocorticoid-monokine interactions so that the perturbation in
glucocorticoid action during endotoxic shock may possibly be
reversed with therapeutic intervention.  This, in turn, will lead to
improved survival from a very serious and life-threatening clinical
syndrome.

## Key facts

- **NIH application ID:** 3129903
- **Project number:** 5R01AI020322-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **SAM.gov UEI:** GY8NMUZQXVS7
- **Principal Investigator:** RODERICK E MCCALLUM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $122,724
- **Award type:** 5
- **Project period:** 1984-03-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129903

## Citation

> US National Institutes of Health, RePORTER application 3129903, STEROID ACTION IN BACTERIAL ENDOTOXIC SHOCK (5R01AI020322-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129903. Licensed CC0.

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