1 7 , 1 3 ; 2 40 w w w . r e a n i m a t o l o g y . c o mТенденция к развитию и генерализации инфекции у пациентов с тяжелой термической травмой реали зуется за счет комплексного влияния термической травмы на иммунную систему. Особенно страдает фаго цитарная система, представленная, в первую очередь, нейтрофильными гранулоцитами.Цель исследования: определение динамики изменения функциональной активности нейтрофилов у па циентов с термической травмой, а также ее прогностической значимости при развитии гнойно септических осложнений ожоговой болезни.Материалы и методы. Функциональную активность нейтрофилов оценивали на основе спонтанного и ин дуцированного хемилюминесцентного ответа цельной крови при последовательной стимуляции форбол 12 миристат 13 ацетатом (ФМА) и N формил метионил лейцил фенилаланином (фМЛФ). Было обследовано 34 пациента с ожоговой болезнью при разной тяжести течения ожоговой болезни и в динамике наблюдения.Результаты. Разработанная новая методика была использована для исследования цельной крови паци ентов с ожоговой болезнью, получены данные о функциональной активности нейтрофилов при разной тя жести течения болезни и в динамике. В результате анализа хемилюминесцентных кривых развития респи раторного взрыва нейтрофилов выявлены показатели, характеризующие состояние иммунной системы, а именно: одно-или двухфазный ответ на стимул, удельная активность нейтрофила «быстрой фазы», удель ная активность нейтрофила «медленной фазы».Заключение. Результаты позволили выделить тенденции изменения функциональной активности ней трофилов при ожоговой болезни. Предложены диагностические и прогностические показатели функцио нальной активности нейтрофилов для оценки тяжести болезни и прогноза септического процесса. Ключевые слова: хемилюминесценция; функциональная активность нейтрофилов; ожоговая травма; сепсисA complex effect of thermal trauma on the immune system triggers the tendency to develop and generalize infection in patients with severe thermal trauma. The phagocytic system, which is represented, first of all, by neu trophilic granulocytes, is significantly altered.Objective: to determine the dynamics of changes in the functional activity of neutrophils in patients with thermal trauma, as well as its prognostic significance in the development of purulent septic complications of a burn disease.Materials and methods. The functional activity of neutrophils was assessed by spontaneous and induced chemiluminescence responses of whole blood sequentially stimulated with phorbol 12 myristate 13 acetate ВведениеПроблема лечения ожоговой болезни и ее осложнений не теряет актуальности до настоя щего времени [1]. В структуре летальности тя желообожженных ведущее место занимает ин фекция, приводящая к развитию пневмонии и сепсиса [2]. Развитие и генерализация инфекции у тяжелообожженных реализуется за счет влия ния термической травмы на иммунную систему; в особенности страдает фагоцитарное звено им мунитета [3][4][5]. Дисфункция фагоцитов прояв ляется в нарушении уничтожения бактерий, из менении уровня секреции ин...

Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor alpha (TNF alpha), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, beta-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNF alpha has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response.

Patients with the sepsis syndrome have detectable levels of circulating TNF-alpha, IL-1, IL-6, and lipopolysaccharide independent of culture-documented infection. Lipopolysaccharide and cytokines may play a pathogenic role in sepsis, and the combination of several elevated factors may be important in determining patient survival.

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The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.

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Our current understanding of sepsis and multiple organ dysfunction needs to be revised, as the uniformly negative results of new therapies for these disorders suggest. Previous theories for the pathogenesis of these conditions are incomplete; reasons for this include the following. First, the surrogate models that have been used to study these disorders are not analogous to the clinical situation. Second, patients who have less severe manifestations of these diseases are often overlooked. And third, patients' preexisting conditions have not been taken into account. Considerable new evidence indicates that, in addition to a massive proinflammatory reaction, a compensatory anti-inflammatory response contributes to the onset of these disorders. At a local site of injury or infection and during the initial appearance of pro- and anti-inflammatory mediators in the circulation, the beneficial effects of these mediators outweigh their harmful effects. Only when the balance between these two forces is lost do these mediators become harmful. Sequelae of an unbalanced systemic proinflammatory reaction include shock, transudation into organs, and defects in coagulation. An unbalanced systemic compensatory anti-inflammatory response can result in anergy and immunosuppression. The proinflammatory and anti-inflammatory forces may ultimately reinforce each other, creating a state of increasingly destructive immunologic dissonance.