title: Immune dysfunction in the elderly and its reversal by antihistamines.
abstract: The decline in immunity seen in the elderly is a significant contributor to disease burden. This decline has largely been attributed to alterations in T cell immunity and contributes to an overall increased risk and severity of infection in the elderly. A key component of T cell immunity involves antigen presentation, an event where an antigen is processed and presented to specific immune cells for destruction. This event has been found to be crucial to immune function. Recent research has focused on a key antigen presenting cell (APC), the dendritic cell (DC), and changes within its function associated with aging. DCs are considered to be the most professional APCs, and are responsible for the initiation and outcome of effector T cells and their resultant immune response. DCs capture antigens and undergo a maturation process and polarize into either type 1 dendritic cells (DC1) or type 2 dendritic cells (DC2), based upon their ability to favor a T helper1 (Th1) or T helper 2 (Th2) T cell response, respectively. Evidence suggests that in normal healthy adults, a Th1 type response predominates, and in frail elders, a Th2 response predominates. It has been proposed that this change from a predominately Th1 type to a predominate Th2 type response is a possible mechanism for age-associated immune dysfunction. In addition, recent research has focused on how histamine, an inflammatory mediator, promotes a Th2 response. Histamine has also been shown to polarize human DCs into Th2 cell-promoting effector DCs or DC2s. This has been shown to occur via interaction with the H2 receptor. Therefore, we theorize that use of an H2 selective antihistamine will reverse this polarization back to a Th1 type response and therefore improve immune function of the frail elderly.
authors.affiliation: Department 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
authors.forename: Asif
authors.initials: A
authors.lastname: Rafi
authors.forename: Steven C
authors.initials: SC
authors.lastname: Castle
authors.forename: Koichi
authors.initials: K
authors.lastname: Uyemura
authors.forename: Takashi
authors.initials: T
authors.lastname: Makinodan
mesh_terms: D000375:Aging / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D006634:Histamine H1 Antagonists