# CHEMISTRY AND PHYSIOLOGY OF ENDOGENOUS PYROGENS

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1990 · $180,278

## Abstract

This application has three specific aims:  to establish the
mechanism of Interleukin 1 (IL-1) action on T cells; to establish
the mechanisms of the temperature sensitivity of T cells; and to
purify and characterize an apparently new lymphokine which causes
macrophages to secrete IL-1.

Current work has suggested that exposure of LBRM IA5 cells to IL-
l cause increased phosphorylation of lipocortin, a cell membrane
protein which regulates phospholipase A2 (PLA-2) activity.  It is
proposed to extend this work by repeating it with other cell lines
with both IL-1 alpha and beta, and using a variety of different
incubation times and adjunct stimuli.  The possible involvement of
an N protein in the stimulus chain will be investigated using
pertussis and cholera toxins.  Available evidence strongly suggests
that many IL-1 actions are mediated by arachidonic acid
metabolites.  Since IL-1 action is thought to be deleterious in
some circumstances, such as during acute sepsis, knowledge of the
pathways of cell activation by IL-1 might allow effective
therapeutic interventions.

It is already known that IL-1 action is strongly enhanced by small
increases in temperature, and current work has shown that one
mechanism for this is greatly enhanced secretion of Interleukin 2
by IL-l stimulated T cell lines.  lt is proposed now to investigate
the effect of temperature on IL-2 receptor expression by T cells,
and on the lipocortin phosphorylation and PLA-Z activation
discussed above.  The most probable cause of an unusually high
temperature sensitivity is a lipid phase change, and these membrane
events might well depend on the fluidity of the cell membrane, or
its inner half.

Purification of the lymphokine will be attempted using sizing, ion
exchange, isoelectric focusing and reverse phase columns on a
pharmacia FPLC system.  The molecular properties of the purified
activity will be compared to those of known lymphokines, and if it
appears to be truly new an attempt will be made to develop
monoclonal antibody and use it to identify the cDNA for the gene
in a T cell expression library.

## Key facts

- **NIH application ID:** 3124155
- **Project number:** 5R01AI003772-28
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** PATRICK A MURPHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $180,278
- **Award type:** 5
- **Project period:** 1977-01-01 → 1990-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124155

## Citation

> US National Institutes of Health, RePORTER application 3124155, CHEMISTRY AND PHYSIOLOGY OF ENDOGENOUS PYROGENS (5R01AI003772-28). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124155. Licensed CC0.

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