Alteration of drug biotransformation and elimination during infection and inflammation

Area of Science:

• Biochemistry
• Pharmacology
• Immunology

Background:

• Cytochrome P450 (CYP) enzymes are crucial for drug and endogenous substance metabolism.
• Infection and inflammation significantly alter CYP expression and activity.
• Cytokines are key mediators in the inflammatory response affecting CYP pathways.

Purpose of the Study:

• To review the impact of infection and inflammation on major mammalian CYP families.
• To explore the mediator pathways responsible for CYP down-regulation.
• To understand the link between central nervous system (CNS) inflammation and peripheral CYP changes.

Main Methods:

• Literature review of studies on CYP expression during infection/inflammation.
• Analysis of pre-translational modifications affecting CYP isoforms.
• Investigation of cytokine involvement in CYP regulation.
• Examination of CNS-to-periphery signaling pathways.

Main Results:

• Infection/inflammation leads to modified CYP expression and biotransformation capacity.
• CYP isoforms are often regulated at the pre-translational level, with cytokine involvement.
• CNS inflammation causes a loss of CYP in the brain.
• A signaling pathway connects CNS inflammation to peripheral CYP down-regulation.

Conclusions:

• Inflammation-induced changes in CYP impact liver drug handling and endogenous substance metabolism.
• Cytokine-mediated pathways are central to CYP alterations during infection/inflammation.
• Understanding these pathways is critical for managing drug therapy and physiological balance during inflammatory conditions.