Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. It is likely that disordered immune mechanisms and/or defective regulation of inflammatory responses are central to the pathological processess which result in tissue injury in MS. Prostaglandins (PGs) and other products of arachidonic acid (C20:4) metabolism are important regulators of cell function and local mediators of inflammation. While the evidence is equivocal, PG regulation of immune function may be altered in MS patients. We have shown that increased lymphocyte adherence (virus infected cells and myelin) in MS patients may be due to a monocyte dependent, and prostaglandin E mediated mechanism and that MS monocytes spontaneously produce increased levels of PGE in tissue culture. Thus, increased lymphocyte adherence may be in an in vitro measurement of a monocyte controled PGE modulation of a T-cell response (adherence). It is possible that PG-mediated modulation or control of lymphocyte cell surface receptors can, in part, account for much of the immunologic epiphenomena observed in MS. We will continue to delineate mechanisms which govern lymphocyte adherence to myelin and will evaluate peripheral blood monocytes, monocyte function and arachidonic acid metabolism in MS. In particular, these studies will include evaluation of arachidonic acid metabolism in MS monocytes, CSF leukocytes and their relation to lymphocyte adherence to myelin. Results will be correlated with clinical features. Further, as an extension of our studies, we will examine monocyte function, Ia antigen expression and the role of monocytes in lymphocyte adhesion. It is likely that these studies will provide useful new information on monocyte-prostaglandin interactions and their role in altered leukocyte function in multiple sclerosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS014357-06
Application #
3395507
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1979-12-01
Project End
1988-11-30
Budget Start
1985-12-01
Budget End
1988-11-30
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Medicine
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
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