HUMAN INTERLEUKIN-1 INHIBITOR

Project: Research project

Project Details

Description

A specific inhibitor of Interleukin-1 (IL-1) in humans has recently been
identified that is present in the urine of some normal individuals, but is
found in elevated amounts in the urine of patients with fever and certain
other pathological conditions. It is a glycoprotein of approximately 30
Kd. that specifically inhibits (IL-1) induced thymocyte proliferation, but
also interacts with IL-1 in its effects on fibroblast prostaglandin
synthesis. The proposed study is a comprehensive analysis of the
structure, physiology, and function of this newly described molecule.

A biochemical purification scheme using a variety of chromatographic
procedures will be developed in order to purify the IL-1 inhibitor to
homogeneity. Purified inhibitor will be used for structural analyses
employing either standard biochemical methods or molecular cloning
methodology. Purified inhibitor will also be used to produce polyclonal or
monoclonal, monospecific antibodies. These antibodies will be utilized to
set up a sensitive and specific immunoassay for the inhibitor. The
spectrum of activity of the IL-1 inhibitor will continue to be
investigated, by analyzing its effects on a number of IL-1 mediated events
in vitro including fibroblast prostaglandin and collagenase synthesis,
hepatocyte production of acute phase serum proteins, and T cell
activation. Its effect in vivo will also be investigated utilizing assays
for IL-1 induced pyrogenicity and adjuvanticity. Its immunosuppressive
effects on in vivo cell mediated and humoral immunity will also be
analyzed. The mechanism of action of the inhibitor will be investigated,
including its effect on IL-1 induced expression of IL-2 receptors or IL-2
production, and cell cycle shift, as well as the role of arachidonic acid
metabolism. Potential effects on the IL-1 molecule itself including direct
binding or prevention of IL-1 interaction with target cells will also be
studied. The cell source of the IL-1 inhibitor will also be determined, as
well as its relationship to acute phase serum proteins, other urine or
serum proteins, and other IL-1 inhibitors.

The long range objectives of this study are to determine the mechanism and
role of the inhibitor as a physiological regulator of immunity and
inflammation in humans.
StatusFinished
Effective start/end date4/1/863/31/87

Funding

  • National Institute of Allergy and Infectious Diseases

ASJC

  • Drug Discovery
  • Biochemistry
  • Toxicology
  • Pharmacology
  • Immunology

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