Differential central nervous system responses following single and multiple recombinant interleukin-2 infusions

Area of Science:

• Neuroscience
• Immunology
• Vascular Biology

Background:

• Recombinant human interleukin-2 (rIL-2) is used therapeutically.
• The impact of rIL-2 on the central nervous system, particularly cerebrovascular integrity, requires detailed investigation.

Purpose of the Study:

• To evaluate the effects of single and multiple systemic rIL-2 infusions on cerebrovascular permeability to immunoglobulin G (IgG) in a rat model.
• To examine ultrastructural changes in cerebral vasculature and brain parenchyma following rIL-2 administration.

Main Methods:

• Rats received single or multiple intravenous infusions of rIL-2.
• Cerebrovascular permeability to IgG was assessed at 6 and 24 hours post-infusion.
• Ultrastructural analysis of cerebral vasculature and brain parenchyma was performed.

Main Results:

• A single rIL-2 infusion moderately increased IgG permeability at 6 and 24 hours, which was not seen after 5 days of infusion.
• Cerebrovascular morphological alterations were observed as early as 6 hours after a single rIL-2 infusion.
• Structural changes, including axonal degeneration and demyelination, persisted and became more widespread with repeated rIL-2 infusions, affecting neuronal and glial cells.

Conclusions:

• Systemic rIL-2 can transiently disrupt the blood-brain barrier, increasing permeability to macromolecules like IgG.
• Repeated rIL-2 administration leads to persistent structural damage in the brain's vasculature and parenchyma.
• These findings highlight potential neurotoxic effects of rIL-2 therapy that warrant further investigation.