Interleukin 1 reduces opioid binding in guinea pig brain

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Interleukin 1 (IL1) is a key mediator of fever and acute-phase responses, originating from macrophages.
• Elevated beta-endorphin levels during fevers suggest a role for opioids in modulating IL1 effects within the central nervous system (CNS).

Purpose of the Study:

• To investigate the influence of purified human Interleukin 1 (IL1) on the binding of various opioid ligands to receptors in different regions of the guinea pig brain.
• To determine if endotoxin (LPS) also affects opioid receptor binding.

Main Methods:

• Purified human IL1 was incubated with membrane preparations from various guinea pig brain regions (cortex, hypothalamus, midbrain, pons, medulla, cerebellum).
• The binding of prototypic opioid agonists (DAME, EKC, DHM) and an antagonist (naloxone) to opioid receptors was measured.
• The effect of endotoxin (S. enteritidis) on opioid ligand binding was also assessed.

Main Results:

• IL1 significantly reduced the binding of opioid ligands to their receptors in multiple brain regions after a 30-min incubation.
• The extent of IL1's inhibitory effect varied by brain region and by the specific opioid ligand tested.
• IL1's effect on dihydromorphine binding in the cortex was dose-dependent.
• Endotoxin (LPS) did not inhibit opioid ligand binding in any tested brain region.

Conclusions:

• Interleukin 1 (IL1) directly interacts with opiate receptors in the guinea pig brain.
• This interaction is not confined to the hypothalamus but occurs in other brain regions as well, indicating a widespread effect.
• IL1's modulation of opioid receptor binding may be a significant mechanism in its CNS actions.