Holzheimer R G, Molloy R, Mendez M V, O'Riordain D, Curley P, Nestor M, Collins K, Saproschetz I, Mannick J A, Rodrick M L
Department of Surgery, Brigham and Womens Hospital, Harvard University Medical School, Boston, MA, USA.
Eur J Surg. 1995 Nov;161(11):795-803.
To find out if an infective challenge caused by a burn followed by caecal ligation and puncture in mice caused more abnormalities of the immune response than burn alone or caecal ligation and puncture alone.
Laboratory study.
University hospital, USA.
80 male 7-8 week old A/J mice.
Burn followed 10 days later by caecal ligation and puncture (n = 18), caecal ligation and puncture alone (n = 24), burn alone (n = 20), and controls (n = 18). The mice had their spleens removed on day 11 (n = 28; 6, 8, 8, and 6 in the respective groups), day 12 (n = 26; 6, 8, 6, and 6), and day 13 (n = 26; 6, 8, 6, and 6), and splenocytes and adherent cells were harvested for measurement of prostaglandin E2 (PGE2), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha).
Alterations in the production of the cytokines.
After the double challenge (burn followed by caecal ligation and puncture) there were significant reductions in production of TNF-alpha and IL-6 compared with caecal ligation and puncture alone (p < 0.05), burn alone (p < 0.05), and controls (p < 0.05). These findings indicate that activation of macrophages was reduced after infection; production of TNF-alpha, IL-1, and IL-6 by splenocytes stimulated by lipopolysaccharide was reduced.
The differences do not seem big enough to indicate that mortality would be increased after caecal ligation and puncture alone. Only when there has been a previous injury (which resulted in hyperactivation of macrophages followed by a more pronounced hypoactivation) would mortality increase. In view of clinical trials with antiendotoxin and antiTNF antibodies that failed to improve survival in infected patients, we suggest that the mechanisms of the cellular immune response need further clarification.
探究在小鼠中，烧伤后继以盲肠结扎和穿刺所引发的感染性刺激，是否比单纯烧伤或单纯盲肠结扎和穿刺导致更多的免疫反应异常。
实验室研究。
美国大学医院。
80只7 - 8周龄的雄性A/J小鼠。
10天后进行烧伤后继以盲肠结扎和穿刺（n = 18）、单纯盲肠结扎和穿刺（n = 24）、单纯烧伤（n = 20）以及对照组（n = 18）。在第11天（n = 28；各实验组分别为6只、8只、8只和6只）、第12天（n = 26；各实验组分别为6只、8只、6只和6只）和第13天（n = 26；各实验组分别为6只、8只、6只和6只）摘除小鼠脾脏，收获脾细胞和黏附细胞，用于测量前列腺素E2（PGE2）、白细胞介素1（IL - 1）、白细胞介素2（IL - 2）、白细胞介素6（IL - 6）和肿瘤坏死因子α（TNF - α）。
细胞因子产生的变化。
与单纯盲肠结扎和穿刺（p < 0.05）、单纯烧伤（p < 0.05）及对照组（p < 0.05）相比，双重刺激（烧伤后继以盲肠结扎和穿刺）后TNF - α和IL - 6的产生显著降低。这些发现表明感染后巨噬细胞的活化降低；脂多糖刺激脾细胞产生TNF - α、IL - 1和IL - 6减少。
这些差异似乎不足以表明单纯盲肠结扎和穿刺后死亡率会增加。只有先前存在损伤（导致巨噬细胞过度活化，随后出现更明显的低活化）时死亡率才会增加。鉴于抗内毒素和抗TNF抗体的临床试验未能提高感染患者的生存率，我们建议细胞免疫反应的机制需要进一步阐明。
