# GLUCOCORTICOSTEROID ACTION IN INFLAMMATORY DISEASE

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1987 · $162,765

## Abstract

The objective is an increased understanding of the mechanism by which
antiinflammatory steroids alleviate allergic diseases in man.  These
studies represent the logical outgrowth of our initial studies, which
showed that:  1) steroids prevent the release of histamine and
sulfidopeptide leukotrienes from human basophils, 2) steroids do not
inhibit the release of inflammatory mediators from purified human lung mast
cells, 3) steroids inhibit the release of cyclooxygenase metabolites from
nonmast cell sources in human lung fragments and from monocytes purified
from blood, 4) steroids inhibit the unstimulated binding of purified human
neutrophils (PMN) to monolayers of human vascular endothelial cells (VEC)
but do not inhibit the stimulus-induced binding of PMN to VEC, 5) human
lung fragments release a material which induces VEC to become adhesive,
causing marked increases in PMN adherence, and 6) steroids inhibit the
release of this adhesiveness-inducing activity from human lung fragments.
Studies in this proposal are aimed at establishing the in vivo relevance of
the inhibitory steroid action on human basophils.  We will further explore
the mechanism of this effect and characterize a leukocyte-derived
antagonist.  We will determine whether steroids prevent the release of
arachidonic acid metabolites from human cells (e.g., eosinophils,
monocytes, lung fragments, etc.) by inducing the synthesis of a
phospholipase A2 inhibitor such as has been identified in animal studies.
Since steroid therapy in vivo blocks the "late phase reaction" (LPR)
following antigen challenge in man, studies are planned to establish an in
vitro model of the LPR in which products of purified human lung mast cells
will be tested for their ability to initiate adherence of purified human
leukocytes (especially neutrophils and eosinophils) to monolayers of
cultured human VEC.  With such a model system, we will study in vitro the
mechanism by which steroids prevent the accumulation of leukocytes during
the LPR.  These experiments will be designed to establish whether the
steroid action is expressed on the leukocyte, the VEC, or both.  We will
characterize the lung fragment-derived factor which induces adhesiveness of
VEC.  These studies will be aimed at assessing the role of such a factor in
inducing the LPR as well as exploring the hypothesis that inhibition of the
release of the factor is an important antiinflammatory mechanism of
steroids.  It is our opinion that an increased understanding of the
mechanism of antiinflammatory steroid action will result in a better
understanding of inflammatory diseases and aid in the development of new
therapeutic agents.

## Key facts

- **NIH application ID:** 3156128
- **Project number:** 5R01AR031891-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** Robert P Schleimer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $162,765
- **Award type:** 5
- **Project period:** 1983-09-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156128

## Citation

> US National Institutes of Health, RePORTER application 3156128, GLUCOCORTICOSTEROID ACTION IN INFLAMMATORY DISEASE (5R01AR031891-05). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156128. Licensed CC0.

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