# ROLE OF OMEGA-3 FATTY ACIDS IN RHEUMATOID ARTHRITIS

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 1987 · $194,602

## Abstract

Rheumatoid arthritis (RA) is a disabling disease of joint inflammation
affecting about 2%  of adult Americans.  Polymorphonuclear leukocytes (PMN)
and monocytes present in the synovial fluid of rheumatoid joints generate
reduced oxygen species and release proteases which contribute to the
destruction of articular cartilage.  The 5-lipoxygenase (5-LO) pathway of
arachidonic acid (AA) metabolism leads to the production of leukotriene
(LT) B4 in PMN and monocytes, and LTC4, LTD4 and LTE4 in monocytes and
eosinophils.  LTB4 is chemotactic for PMN and monocytes and can also cause
granule and superoxide release from these cells.  LTC4, LTD4 and LTE4 cause
arteriorlar constriction and contraction of epithelial cells leading to
fluid transudation and accumulation of proteins in extravascular
compartments.  Decreasing the production of LTs or substituting the
production of the biologically less active pentaene analog, LTB5, could be
a useful, specific, and potentially non-toxic mechanism of controlling
joint inflammation.  Our aim is to identify the role of a Omega-3 fatty
acids (Omega-3FA) in altering the clinical course of RA, and to seek
relationships with alterations in the cell biology and biochemistry of the
5-LO pathway of AA metabolism and of platelet activating factor (PAF)
generation in leukocytes.  The first goal will be to determine the effect
of ingestion of Omega-3FA on the clinical course of RA and to seek
relationships between clinical effects with the net production of 5-LO
products and production of PAF in response to calcium ionophore A23187,
generation of pentaene 5-LO products, and changes in chemotaxis by
peripheral blood PMN, and to correlate changes with the lipid composition
of these cells.  5-LO products will be analyzed by radioimmunoassay and
high performance liquid chromatography.  The second goal will be to examine
the effect of incorporation of Omega-3FA on the ability of monocytes, PMN,
and eosinophils to produce 5-LO products in response to the transmembrane
stimulus zymosan for PMN and monocytes, and
formyl-methionyl-leucyl-phenylalanine for eosinophils.  The third goal is
to determine the mechanism by which incorporation of Omega-3FA into cell
membranes alters release of AA from the cell membranes of PMN of normal
volunteers; by examining the controls and properties of PMN phospholipase
A2 function and by purification of the enzyme beginning with fast protein
liquid chromatography ion exchange and gel filtration techniques.  The
fourth goal is to identify specific differences in the enzymatic metabolism
of LTB4 and LTB5 and their 20-PH derivatives.

## Key facts

- **NIH application ID:** 3158671
- **Project number:** 1R01AR038638-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **SAM.gov UEI:** QN6MS4VN7BD1
- **Principal Investigator:** Roy Soberman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $194,602
- **Award type:** 1
- **Project period:** 1987-05-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158671

## Citation

> US National Institutes of Health, RePORTER application 3158671, ROLE OF OMEGA-3 FATTY ACIDS IN RHEUMATOID ARTHRITIS (1R01AR038638-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3158671. Licensed CC0.

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