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Immune dysfunction in the elderly and its reversal by antihistamines
Asif Rafi1, Steven C Castle, Koichi Uyemura
1Department of Medicine, University of California at Los Angeles School of Medicine, 11301 Wilshire Boulevard, Building 220, Room 312, Los Angeles, CA 90073, USA. arafi@mednet.ucla.edu
Summary
Aging impairs immunity by shifting T cell responses. H2 antihistamines may reverse this, promoting a Th1 response and improving immune function in the elderly.
Area of Science:
- Immunology
- Gerontology
Background:
- Age-related immune decline increases infection risk and severity in the elderly.
- T cell immunity, crucial for defense, is altered with aging, particularly antigen presentation by dendritic cells (DCs).
- DCs polarize into DC1 (Th1 response) or DC2 (Th2 response); frail elders show a predominant Th2 response, unlike healthy adults' Th1 response.
Purpose of the Study:
- To investigate the role of histamine in age-associated DC polarization.
- To determine if H2 selective antihistamines can reverse Th2 polarization in DCs.
- To explore the potential of H2 antihistamines in improving immune function in the frail elderly.
Main Methods:
- Analyzing DC polarization in aging individuals.
- Investigating histamine's effect on DC polarization via H2 receptors.
- Theorizing the use of H2 selective antihistamines to modulate DC polarization.
Main Results:
- Histamine promotes Th2 responses by polarizing DCs into DC2s through H2 receptor interaction.
- A shift from Th1 to Th2 response is observed in frail elders, potentially explaining immune dysfunction.
- Evidence suggests histamine actively drives this detrimental Th2 polarization.
Conclusions:
- Histamine-induced Th2 polarization of DCs contributes to age-associated immune dysfunction.
- H2 selective antihistamines are proposed as a therapeutic strategy to reverse Th2 polarization.
- Targeting histamine signaling may restore a protective Th1 immune response in the elderly.