UMLS:C0243026 - FACTA Search

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Query: UMLS:C0243026 (sepsis)
52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Suppression of cellular immunity and increased susceptibility to sepsis frequently accompany thermal injury. However, a convincing association between the two has been difficult to establish in human beings. Therefore we chose to investigate the relationship of impaired cell-mediated immunity with susceptibility to sepsis in an animal model. We studied the response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production by splenocytes from mice subjected to a standard 25% scald burn and killed at intervals of 3, 5, 7, 10, 14, and 25 days after thermal injury. Burned mice were compared in all instances to sham-burn animals (i.e., animals that had been anesthetized and shaved but not burned). We also studied mortality after cecal ligation and puncture (CLP), as a septic challenge, in burned and control animals at the same postburn intervals. We found maximal suppression (50% to 55%) of the PHA response at 10 to 14 days after injury and maximum suppression (68%) of IL-2 production at 7 days. Both of these parameters returned to normal by postinjury day 28. Mortality after CLP increased gradually from control levels after thermal injury up to a maximum of 88% on postburn day 10 and also returned to control levels after 28 days after burn. Significant correlations were found between mortality after CLP in the postburn period and suppression of the PHA response, on the one hand, and the suppression of IL-2 production, on the other (r = 0.89 and 0.91, respectively; p less than 0.05). This result implies a causal relationship between impaired cell-mediated immunity and susceptibility to sepsis after burn injury.
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PMID:Temporal correlation of impaired immune response after thermal injury with susceptibility to infection in a murine model. 326 7

Blood small lymphocyte (not exceeding 7.5 micron in diameter) counts obtained from patients with malignant bone tumors in the course of primary examination were 40-75% those in healthy subjects. The said changes were registered only in some patients with osteoblastoclastoma; they were not observed in cases of trauma, osteomyelitis, sepsis, spontaneous osteolysis and chronic synovitis. The study failed to establish a correlation between blood small lymphocyte count, on the one hand, and concentrations of total, stable and active T-lymphocytes as well as autologous E-rosettes, on the other. In the course of separation of lymphocytes in percoll density gradients, small lymphocytes concentrated in high density fractions. Purified small lymphocytes of healthy subjects appeared to be mainly T-lymphocytes, particularly, "activated" ones. Proliferative response to PHA and production of interleukin-2 in cell cultures showing high levels of small lymphocytes were higher than in those with moderate or low concentration of the said cells. Small lymphocytes are considered to be a special subset of T-cells which exhibit high functional activity and may be identified only morphologically. Lowered counts of these cells are attributed to neoplastic growth.
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PMID:[Decreased count of small lymphocytes in the blood of patients with malignant bone tumors]. 349 33

Several theories have been advanced in an effort to explain immunologic suppression after thermal injury, that is monocyte production of immunoregulatory prostaglandins, activation of suppressor cells, production of suppressive serum factors and alteration in helper cell function. In the current study, cytofluorometric analysis was performed on peripheral blood mononuclear cells isolated from 30 severely burned individuals using a FACS IV cell sorter. Fluorescein labeled monoclonal antibodies were used to phenotype total T cells (OKT3+), helper cells (OKT-4+), suppressor cells (OKT-8+), monocytes (antimono.2+) and B cells (anti-Ia+). After burn injury, the most striking phenotypic alterations observed were a marked decrease in the number and percentage of total OKT3+ T cells and OKT4+ helper cells. No significant increases were observed in the OKT8+ suppressor cell subpopulation. Monocytes exhibited a transitory increase during the first 48 hours postburn which returned to normal by postburn day 7. The percentage of Ia+ cells were either normal or decreased in number during the course of the injury. An OKT-4 to OKT-8 ratio of less than 1.00 at 24 to 48 hours postburn may represent a reliable predictive index for death by sepsis. These data suggest that the syndrome of burn induced immunologic suppression may be better described as a "burn induced immunodeficiency syndrome," that is characterized by decreased numbers or function of Interleukin-2 producing helper cells, or both.
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PMID:Flow cytometric analysis of lymphocyte subpopulations after thermal injury in human beings. 623 69

Immunoregulatory cytokines have been implicated in the pathophysiology of graft dysfunction after heart transplantation (HTx). In 15 consecutive patients undergoing HTx we prospectively determined levels of interleukin-6 (IL-6), tumor-necrosis-factor-alpha (TNF-alpha), interleukin-2 (IL-2), and soluble-interleukin-2-receptor (sIL-2-R) at eight points in time during biopsy and right heart catheterization and within 12 hr of echocardiography during the first three months after HTx. Blood was taken from the pulmonary arterial line. IL-6-levels correlated positively with hemodynamic and echocardiographic parameters of pump dysfunction--namely, pulmonary capillary wedge pressure, pulmonary arterial pressure, right atrial pressure, heart rate--and negatively with isovolumic relaxation time and stroke volume independent of the degree of cellular rejection as classified by the ISHLT criteria. A similar pattern was found for TNF-alpha- and sIL-2-R, while IL-2 correlated negatively with left and right heart filling pressures and positively with fractional shortening. In the three patients who died of sepsis or multiorgan failure within the study period IL-6-, TNF-alpha, and sIL-2-R-levels were elevated and IL-2-levels were suppressed compared with the 12 patients with a stable clinical course. IL-6 and sIL-2-R correlated positively while IL-6 and IL-2 correlated negatively. In this pilot study, a cytokine pattern with elevated levels of IL-6, TNF-alpha, and sIL-2-R as well as suppressed levels of IL-2 in the early period after HTx corresponds to impaired hemodynamics independent of cellular rejection and may indicate an unfavorable prognosis. These cytokines may therefore be useful for monitoring and warrant further study.
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PMID:The relation of interleukin-6, tumor necrosis factor-alpha, IL-2, and IL-2 receptor levels to cellular rejection, allograft dysfunction, and clinical events early after cardiac transplantation. 748 19

A number of studies have suggested that the inflammatory and chemotactic autocoid platelet activating factor (PAF), together with various cytokines, plays an important role in the pathophysiology of trauma, sepsis, and shock. However, little is known about PAF's contribution to the immunosuppression associated with hemorrhage. The aim of our study was, therefore, to determine if the use of a PAF-antagonist following hemorrhage has any salutary effects on splenocyte lymphokine production. To study this, mice were bled to and maintained at a mean arterial pressure of 35 mm Hg for 60 min. The mice were then segregated into three groups and were resuscitated with shed blood plus lactated Ringer's solution (2x the volume of shed blood), containing either a potent PAF-antagonist (Ro 24-4736, a thienodiazepine) in dimethyl sulfoxide (DMSO) or DMSO-vehicle. Sham-operated mice received either DMSO-vehicle in saline or saline alone. Twenty-four hours thereafter the animals were sacrificed and splenocyte cultures established and stimulated for 48 hr with Con A (2.5 micrograms/ml). Supernatant lymphokine levels were determined by bioassay. The cellular release of interleukin-2 and -3 (IL-2 and IL-3) by splenocytes was significantly depressed in the nontreated or vehicle-treated hemorrhaged animals compared to shams. Treatment with the PAF-antagonist Ro 24-4736 restored IL-2 and IL-3 release values to levels comparable to those of the sham-operated animals. Thus, (1) PAF appears to play a significant role in hemorrhage-induced immunosuppression and (2) the use of a PAF-antagonist to uncouple the PAF-generated feedback loops prevents the depression in splenocyte function following hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PAF-antagonist administration after hemorrhage-resuscitation prevents splenocyte immunodepression. 764 95

Clinical trials of Russian yeast recombinant human interleukin-2 (yrIL-2) were carried out in 17 patients with posttraumatic and postoperative sepsis to whom 33 intravenous drip infusions of the drug were administered as a single infusion or courses of 2 to 4 injections in a dose of 1,000,000 U per .1 m2 body surface. A positive clinical effect of yrIL-2 in this dose was observed on the next day after the first injection of the drug: the signs of intoxication were reliably reduced. The immunostimulating effect of yrIL-2 consisted in activation of pharmacytizing leukocytes of blood. Addition of yrIL-2 to therapeutic complex for patients with sepsis helped reliably reduce the mortality of such patients with sepsis helped reliably reduce the mortality of such patients to 29.4% vs. 63.3% in controls.
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PMID:[Interleukin-1 in combined detoxification therapy of surgical sepsis]. 773 74

Newborns present a certain degree of immunological immaturity, which makes them highly susceptible to infection. As interleukin-2 (IL-2) is a cytokine that increases the immune response, we performed this study with the object of determining whether there are differences in the serum levels of IL-2 in healthy newborns and those affected by neonatal sepsis in order to establish if there is an increase in the production of IL-2 in systemic neonatal infection. We studied three groups of newborns: group 1-20 healthy full-term newborns; group 2-19 healthy preterm newborns; and group 3-11 infected newborns. The study was performed before the seventh day of life. IL-2 levels were determined by radioimmunoassay (RIA). Covariant analysis showed no significant differences in IL-2 values between the healthy groups (1 + 2) and the infected group (3) (p = 0.7814).
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PMID:Assessment of interleukin-2 (IL-2) in sera of healthy and infected newborns. 773 17

In view of the immunosuppressive action of glucocorticoids (GCs), the activation of the hypothalamo-pituitary-adrenal axis in patients with sepsis or septic shock is paradoxical. At the same time, administration of GCs to these patients is not clearly beneficial. We investigated the role of GCs in severe illness by measuring the sensitivity of peripheral blood mononuclear leukocytes to GCs in a mitogen-stimulated lymphocyte proliferation assay. In addition, we studied the role of interleukin-2 and several other cytokines in this system. Cells from patients with sepsis or septic shock (n = 15) were more sensitive to the antiproliferative action of GCs than were cells from normal controls (IC50 6.7 +/- 2.1 nmol/L for patients vs. 19.5 +/- 2.5 nmol/L for controls; P < 0.01). This increased sensitivity of the peripheral mononuclear cells to dexamethasone during the period of sepsis normalized during the ensuing period of clinical recovery of these patients. Dexamethasone inhibited the production of interleukin-2 in the mitogen-stimulated cells. Addition of interleukin-2 antagonized the suppressive effects of dexamethasone in a dose-dependent manner, both in cells from controls and in cells from patients with sepsis. To a lesser extent, the combination of interleukin-1, interleukin-6, and tumor necrosis factor-alpha also counteracted the effects of dexamethasone. In conclusion, our results suggest that not only the activity of the hypothalamo-pituitary-adrenal axis but also the sensitivity to GCs is regulated during sepsis and septic shock. Generally there is an increased sensitivity to GCs, which might help to protect the organism as a whole through supportive effects on metabolism and vasculature. This hypersensitivity is counteracted, possibly at the site of inflammation, by high local concentrations of cytokines. This would enable an adequate local response of the immune system in the presence of elevated cortisol levels. In view of the increased sensitivity of peripheral leukocytes to GCs, treatment of these patients with high doses of GCs may not be beneficial or may even be harmful.
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PMID:Differential adaptation of glucocorticoid sensitivity of peripheral blood mononuclear leukocytes in patients with sepsis or septic shock. 777 26

Activation of the complement and contact systems occur in patients with septic shock and is associated with a poor outcome. Activation of both systems is regulated by a common inhibitor, C1-esterase inhibitor (C1-Inh). Functional levels of C1-Inh are normal or slightly decreased in septic patients although this inhibitor is an acute phase protein. Moreover, an increased turn-over of C1-Inh in sepsis likely occurs since levels of proteolytically inactivated ("modified") C1-Inh are increased in this syndrome. One may therefore postulate that in sepsis there is a relative deficiency of C1-Inh. Here we will summarize our preliminary studies in 11 patients with septic shock, who received high doses of C1-Inh for up to 5 days. Activation of complement and contact systems also occurs in "a human model for septic shock" i.e., the vascular leak syndrome (VLS) induced by immunotherapy with the cytokine interleukin-2 (IL-2). The similarity between VLS and sepsis is not only reflected by similar patterns of complement and contact activation, but also by comparable hemodynamic and biochemical changes, and by the involvement of a number of other inflammatory mediators, such as the release of pro-inflammatory cytokines, and activation of coagulation and fibrinolysis and of neutrophils. Here we will also summarize our initial studies of the effect of C1-Inh administration to 6 patients with the VLS induced by IL-2. Our results indicate that high doses of C1-Inh can be safely administered to patients with septic shock or with the VLS, and may attenuate complement and contact activation in these conditions. Whether this therapy may reduce mortality and or morbidity of either syndrome has to be established by double-blind controlled studies.
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PMID:Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy. 783 67

C1-inhibitor (C1-INH) is the major plasma inhibitor of the complement and contact systems. Activation of either system has been shown to occur in patients with septic shock and is associated with a poor outcome. Functional levels of C1-INH tend to be normal in septic patients although paradoxically this inhibitor is an acute phase protein. Moreover, levels of proteolytically inactivated C1-INH are increased in sepsis pointing to an increased turn-over. These observations suggest a relative deficiency of biologically active C1-INH in sepsis. Complement and contact activation have also been shown to occur in the vascular leak syndrome (VLS) induced by immunotherapy with the cytokine interleukin-2 (IL-2), which syndrome may be regarded as a human model for septic shock. The similarity between VLS and sepsis encompasses more than complement and contact activation since a number of other inflammatory mediators considered to play a role in the pathogenesis of septic shock, are also involved in the development of VLS. The role and the mechanisms of complement and contact activation in sepsis and in the VLS are reviewed in this paper. Initial results of intervention therapy with high doses of C1-INH in these syndromes are also reported. It is concluded that high doses of C1-INH can be safely administered to patients with septic shock or with the VLS and may attenuate complement and contact activation in these conditions. Double-blind controlled studies are needed to definitely proved these effects and to establish whether this treatment is able to reduce mortality and morbidity of these syndromes.
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PMID:C1-inhibitor substitution therapy in septic shock and in the vascular leak syndrome induced by high doses of interleukin-2. 801 96

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