Immunologic Function in the Elderly After Injury
Immunologic Function in the Elderly After Injury: the Polymorphonuclear Leukocyte (PMN) and Innate Immunity
調査の概要
詳細な説明
Injury in the elderly is characterized by higher mortality rates, longer hospital stays and increased long term disability when controlled for injury severity as compared to the younger cohort of injury patients.(7) The greater likelihood of co-morbid, pre-existing medical conditions, which have a negative impact on outcome, may in part be responsible for this observation. However, there is some disagreement about whether there is an impact of physiologic age as opposed to chronological age on outcomes and whether this is the most important determining factor for the injured elderly. (8) It is clear that the combination of an age factor and baseline health status may determine the ability of the elderly injured patient to recover successfully. This may be due to age related degradation in immune function either PMN related or cell mediated immunity (CMI) related.
In healthy individuals, the metabolic response to hemorrhage, burns and injury is characterized by a hyperdynamic metabolic response that upregulates the proinflammatory/immunologic/metabolic "milieu" and is designed to heal injury, combat infection and prevent death. This inflammatory response on the part of the patient is both functional and adaptive from a physiologic perspective (9). Aging is known to decrease physiologic reserve and may play a role in altering the ability of the injured elderly patient to mount an adaptive, appropriate, inflammatory response when injured (10). Some evidence exists that documents the age-related decline of immunologic function in the elderly, particularly that portion of the immune response described as cell mediated immunity [CMI] (11). This contributes to the higher increase in infections in the elderly (12). There is also animal model evidence that immune function is worsened when combined with injury (13). Similarly, hemorrhage, burns and injury also depress cell mediated immunity in previously healthy individuals increasing the likelihood of infection and organ system failure as a result (14). Little is known, however, about the nature of the immuno/inflammatory response to injury in the elderly. Therefore, one of the hypotheses of our study is that the aging process attenuates this immuno/inflammatory response process, adversely impacting the function of the nonspecific portion of the immune defense system and the main component of that system, the polymorphonuclear leukocyte (PMN).
The systemic immuno/inflammatory response to hemorrhage, burns and injury is well characterized in young, healthy volunteers and animal models and has been studied extensively (15). The key feature of this response is the attraction of PMNs to the site of injury. These are "mature" PMNs that are present in the peripheral bloodstream that possess a life span of approximately 3-5 days. When activated, these cells are responsible for limiting microbial invasion and promoting wound healing. However, prolonged activation of these cells is deleterious as it can lead to perpetuation of the inflammatory response, exacerbating tissue injury and leading to the development of organ system injury, and the condition known as multi-system organ failure. Under normal circumstances, the process of apoptosis, or programmed cellular death, limits the life span of the PMN to 2-3 days and serves to regulate the extent of the immuno/inflammatory response. This allows sufficient time for the acquired immune system to be activated and come on line in response to the cell mediated activity against infection and antigen. Many of the normal functions of the innate, non-specific PMN dependent, immune system are known to be dysfunctional in younger patients who have sepsis, severe injury or shock. It is unclear, however, if the same impact is present in elderly patients who have been injured because little is known about the function of the PMNs in elderly patients in general, and, specifically in those elderly patients who have been injured. Since elderly patients have known, age related depressed cell mediated immunity, our second hypothesis is that there may be age related abnormalities present in the PMNs of elderly patients who have been injured that contribute to the worse outcomes following injury.
The purpose of this study is to begin to characterize the functional status of a portion of the innate immune response following injury in elderly trauma patients. This will be accomplished through analysis of a standard battery of functional tests that characterize PMNs regarding apoptosis and responses to immune challenges. These PMN functionality tests will be correlated with observed clinical outcomes. The null hypothesis for this study is that PMNs from elderly trauma patients have functional characteristics that result in different local and systemic effects than PMN's from non-injured elder controls or non-injured non-elder controls and that this may lead to different effects post injury that impact outcomes.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Ohio
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Akron、Ohio、アメリカ、44304
- Summa Health System
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Greater than 65
- Admitted to the trauma service
Exclusion Criteria:
- Inability to draw sufficient blood
- Immunocompromised
- Currently receiving systemic corticosteroids
- Participation in other studies
- In the opinion of the investigator will not be able to complete protocol
研究計画
研究はどのように設計されていますか?
デザインの詳細
協力者と研究者
スポンサー
捜査官
- 主任研究者:William Fallon, MD、Summa Health System
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
その他の研究ID番号
- 04104
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