It has been thought that there must be covalent binding of low molecular weight drugs, or their metabolites, to larger carrier molecules in order for such drugs and other haptens to stimulate an immune or allergic response. However, since delineation of this mechanism for penicillin allergy was reported over 20 years ago, little progress has been made in identifying reactive metabolites which could initiate allergic responses to other drugs. This project aims to explore the following alternatives: (1) enzyme-inhibitor drugs may stimulate immune responses to drugs when they are firmly bound to their enzymes; (2) host enzymes may covalently link stable drugs with protein carriers, thereby conferring antigenicity; (3) some aspects of drug allergy may be due to drug-induced autoimmune responses, and (4) in vitro binding of drugs or their metabolites to erthrocyte stroma may provide a basis for urgently needed diagnostic tests for drug allergy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032591-03
Application #
3281580
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1983-03-01
Project End
1986-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Wu, C (1986) Conversion of leukotrienes A4 to C4 in cell-free systems. Biochem Biophys Res Commun 134:85-92
Wu, C; Mathews, K P (1986) Generation of drug metabolite antigenicity in the intestinal mucosa. Immunopharmacology 12:53-8