title: Immunosuppression after injury in aged mice is associated with a TH1-TH2 shift, which can be restored by estrogen treatment.
abstract: Aged mice are less likely to survive following traumatic injury and are more immunosuppressed than young mice who sustain comparable injuries. Immunosuppression in severely injured patients is associated with a TH1-TH2 shift. Young mice had robust delayed-type hypersensitivity (DTH) responses after receiving scald or sham injury, whereas the response was diminished in aged sham-injured mice (P < 0.05), and completely absent in aged burn-injured mice (P < 0.01). Production of interferon-gamma (IFN-gamma) did not differ between splenocytes from sham-injured young and aged mice. Splenocytes from burn-injured young and aged mice yielded similar (63-68%) decreases in IFN-gamma, relative to sham-injured mice (P < 0.05). In the absence of injury, cells from aged mice produced 2-fold more interleukin-4 (IL-4) than cells from young (P < 0.01). Interestingly, after burn, less IL-4 was produced by cell from young and aged mice, when compared to age-matched sham-injured animals (P < 0.05). Further studies revealed that estrogen replacement in aged mice restored the post-injury DTH responses (P < 0.05). Interestingly, this restoration paralleled a recovery in IFN-gamma production by splenocytes, but not IL-4 production. Additional studies will be required to determine if age-specific therapies are needed for the treatment of all trauma patients.
authors.affiliation: Immunology and Aging Program, Burn and Shock Trauma Institute, Department of Cell Biology, Neurobiology, and Anatomy, Department of Surgery, Loyola University Medical Center, Stritch School of Medicine, Maywood, IL 60153, USA. ekovacs@lumc.edu
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Duffner
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Plackett
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D002056:Burns / Q000276:immunology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D004967:Estrogens; D015847:Interleukin-4; D007371:Interferon-gamma