Low-Dose Interleukin-2 Reverses Traumatic Brain Injury-Induced Cognitive Deficit and Pain in a Murine Model

Area of Science:

• Neuroscience
• Immunology
• Traumatic Brain Injury Research

Background:

• Mild traumatic brain injury (mTBI) frequently leads to chronic headache and cognitive deficits, with limited effective treatments.
• Early low-dose interleukin-2 (LD-IL-2) administration shows neuroprotective effects against mTBI sequelae.
• A critical gap exists in understanding LD-IL-2 efficacy for established chronic mTBI symptoms.

Purpose of the Study:

• To determine if LD-IL-2 treatment administered long after mTBI can alleviate chronic post-traumatic headache (PTH) and cognitive impairments.
• To investigate the role of regulatory T (Treg) cells in the therapeutic mechanism of delayed LD-IL-2 treatment.

Main Methods:

• mTBI was induced using a noninvasive closed-head weight drop model in mice.
• LD-IL-2 was administered 4-6 weeks post-mTBI to assess effects on PTH behaviors and cognitive function (novel object recognition, object location).
• Regulatory T cells were depleted to elucidate the mechanism of LD-IL-2 action.

Main Results:

• Delayed LD-IL-2 treatment successfully abolished chronic PTH-related behaviors and fully reversed mTBI-induced cognitive deficits in both sexes.
• Depletion of Treg cells exacerbated PTH behaviors and negated the therapeutic benefits of LD-IL-2.
• LD-IL-2 treatment significantly increased Treg cell populations in the dura mater but not within brain tissue.

Conclusions:

• The therapeutic effects of delayed LD-IL-2 treatment for chronic mTBI symptoms are mediated by the expansion of meningeal Treg cells.
• This study identifies Treg cells as a key cellular target and LD-IL-2 as a potential therapy for chronic PTH and cognitive dysfunction following mTBI.
• LD-IL-2 demonstrates a broad therapeutic time window and potential to reduce polypharmacy in mTBI management.