# INFLAMMATORY RESPONSES IN ALLERGIC REACTIONS AND ASTHMA

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1993 · $283,745

## Abstract

Pathogenic mechanisms underlying late phase reactions (LPR) in IgE-
mediated responses in skin and respiratory tract are not well-
defined with roles postulated for activated granulocytes and T
lymphocytes.  Using skin chamber approach overlying developing LPR
to pollen Ag challenge, we have made frequent sequential
assessments, finding characteristic sequential patterns of mast
cell, (MC) and likely basophil, mediator release, accumulation of
activated neutrophils and eosinophils, increased expression of
adhesion molecules on granulocytes and vascular endothelium,
followed by entry of CD4+ lymphocytes.  However, it is still
unclear what initiates these vascular and granulocyte responses and
their relationship to the pathogenesis of LPR.  We will extend
these studies in a group of inter-related projects to learn more
about mechanisms underlying these inflammatory events.  Using a
combination of skin chamber and skin biopsy approaches, we will: 1)
compare patterns of PMN and eosinophil activation, vascular
adhesion molecule expression, mediator release and the presence of
cytokine mRNA and protein in different subjects with and without
LPR developing after similar immediate responses (looking for a
host factor in LPR); 2) determine why the same subject manifest
strong LPR to pollen antigens why codeine induces strong immediate
MC activation and whealing but nosubsequent LPR in the sites; 3)
assess adherence of LPR site granulocytes to matrix proteins; since
such adherence is likely important in leukocyte passage from the
blood into and through the dermis 4) determine the possible role of
T lymphocytes in LPR, - whether there is preferential reactivity of
lymphocytes from LPR sites to the challenge Ag, by Vbeta gene usage
and limiting dilution approaches; also whether this associated with
certain cytokine profiles; 5) study mechanisms underlying
corticosteroid inhibition of LPR.  These studies will utilize
immunoassays, immunohistochemistry, electron microscopy, cell
culture and molecular biology approaches.  The overall hypothesis
being tested is that events following initial MC activation,
including the continued presence of antigen in the site, lead to
release of mediators and cytokines that upregulate accumulation and
activation of granulocytes in the site.  These events may lead to
subsequent accumulation of T cells, which perpetuate the reaction
through cytokine release.  Corticosteroids may inhibit LPR by
suppressing cytokine formation and granulocyte adhesion/activation.
These findings will be considerable clinical important because the
inflammatory response in LPR is thought to play a major role in
chronic allergic diseases.

## Key facts

- **NIH application ID:** 3125689
- **Project number:** 2R01AI014332-17
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** BURTON ZWEIMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $283,745
- **Award type:** 2
- **Project period:** 1977-09-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125689

## Citation

> US National Institutes of Health, RePORTER application 3125689, INFLAMMATORY RESPONSES IN ALLERGIC REACTIONS AND ASTHMA (2R01AI014332-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125689. Licensed CC0.

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