In 1979, we established a prospective study of 300 healthy individuals over age 65, addressing the question of whether depressed cellular immune status acted as an independent risk factor for the subsequent development of morbidity and/or mortality in an otherwise healthy, elderly individual. We have used this same population to study changes in immunoregulation with age. Specifically, we have been addressing the question of whether increased sensitivity to inhibition by the endogenous immunomodulator PGE2 accounts for some of the immunological changes that have been described in aging humans. The goal of this present 5 year renewal is to continue our prospective study of healthy, elderly individuals, at least until there is sufficient mortality and/or total number of morbid events so that we can ask the question in a rigorous fashion as to the possible effects of depressed cellular immune status. In addition, we will be able to address the question of whether manifestations of autoimmunity (autoantibodies, circulating immune complexes) are associated with the increased chance of developing atherosclerosis. We will also continue our studies on the role of endogenous prostaglandin E2 and other aracidonic acid metabolites in the control of humoral and cellular immune responses. We will examine the role of endogenous PGE in antigen-specific immune responses in vitro, using the model of patients chronically infected with Q-fever (coxiella burnettii). We will also examine the role of 15 hydroperoxyeicosatetranoic acid in the generation of suppressor cells in vitro. Finally, we will investigate whether treatment of elderly individuals with non-steroidal anti-inflammatory agents, which inhibit the production of prostaglandin in vivo and in vitro, effect serologic manifestations of autoimmunity.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006086-04
Application #
3116874
Study Section
Immunobiology Study Section (IMB)
Project Start
1985-07-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1989-11-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
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