Kovacs Elizabeth J, Duffner Lisa A, Plackett Timothy P
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.
Mech Ageing Dev. 2004 Feb;125(2):121-3. doi: 10.1016/j.mad.2003.11.007.
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.
与遭受类似创伤的年轻小鼠相比，老年小鼠在创伤性损伤后存活的可能性更小，免疫抑制程度更高。严重受伤患者的免疫抑制与TH1向TH2的转变有关。年轻小鼠在接受烫伤或假伤后有强烈的迟发型超敏反应（DTH），而老年假伤小鼠的反应减弱（P<0.05），老年烧伤小鼠则完全没有反应（P<0.01）。假伤的年轻和老年小鼠的脾细胞产生干扰素-γ（IFN-γ）的情况没有差异。与假伤小鼠相比，烧伤的年轻和老年小鼠的脾细胞产生的IFN-γ减少程度相似（63-68%）（P<0.05）。在未受伤的情况下，老年小鼠的细胞产生的白细胞介素-4（IL-4）比年轻小鼠的细胞多两倍（P<0.01）。有趣的是，与年龄匹配的假伤动物相比，年轻和老年小鼠烧伤后细胞产生的IL-4较少（P<0.05）。进一步的研究表明，老年小鼠补充雌激素可恢复伤后的DTH反应（P<0.05）。有趣的是，这种恢复与脾细胞产生IFN-γ的恢复平行，但与IL-4的产生无关。需要进行更多的研究来确定是否需要针对所有创伤患者的年龄特异性治疗方法。
