# PHOSPHODIESTERASE STUDIES IN ATOPIC DERMATITIS

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 1989 · $153,768

## Abstract

Atopic dermatitis (AD) is a chronically recurrent cutaneous
inflammatory disease which may affect up to 10% of the
population.  The condition is part of the atopic triad which also
includes asthma and allergic rhinitis.  These diseases have strong
hereditary patterns but the genetics is unclear.

AD is characterized by a variety of immunologic and
pharmacologic abnormalities, and evidence from transplant
studies indicates that the basic abnormality is expressed in bone
marrow cells.  Defects such as increased basophil histamine
release and high spontaneous IgE production by B lymphocytes
imply defective cellular regulation.  Abnormalities of cyclic
nucleotide metabolism have been demonstrated in AD and
elevated cAMP-phosphodiesterase (PDE) activity with resultant
low intracellular cAMP levels may have a net permissive effect
on immune and inflammatory responses.  Chromatofocusing
studies of abnormal PDE have demonstrated two distinctly
abnormal cytosolic fractions of PDE activity in monocytes and
lymphocytes.  The recent development of monoclonal antibodies
to PDE's now provides us with the means to characterize and
isolate abnormal enzyme forms.  We will expand upon preliminary
evidence for phosphorylation as a mechanism of PDE activation
and study proteolytic effects on enzyme structure and activity.
We will use immunodetection assays for predictive screening of
atopic individuals and for identifying specific leukocyte subsets.

Another major effort will be directed at induction of leukocyte
activation markers and abnormal PDE mononuclear leukocytes by
immune effector factors produced by AD leukocyte cultures and
potentially by specific cytokines.

Finally we intend to study cord blood leukocytes for elaboration
of activation factors and for abnormal PDE activity as predictors
of atopy and bronchopulmonary dysplasia.

These studies are directed at determining primary events leading
to atopy, to provide biochemical markers of disease and to clarify
abnormal biochemical and immunological mechanisms associated
with increased PDE in atopic dermatitis.

## Key facts

- **NIH application ID:** 3128046
- **Project number:** 5R01AI018615-08
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **SAM.gov UEI:** NPSNT86JKN51
- **Principal Investigator:** JON M HANIFIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $153,768
- **Award type:** 5
- **Project period:** 1982-05-01 → 1991-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128046

## Citation

> US National Institutes of Health, RePORTER application 3128046, PHOSPHODIESTERASE STUDIES IN ATOPIC DERMATITIS (5R01AI018615-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128046. Licensed CC0.

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