Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis is occasionally accompanied by jaundice which is marked by an intrahepatic cholestasis and scant hepatocyte necrosis. The pathogenesis is unknown. The bile fistula rat was used in this study to investigate the possibility that intrahepatic cholestasis is one of the many systemic effects of the major endogenous pyrogen, interleukin-1. The effect of acute administration of endotoxin, interleukin-2 and recombinant rat interferon gamma on biliary secretion and biliary transport mechanisms was also studied. Basal bile flow, peak bile flow and peak sodium taurocholate output were measured after 1 h in all cases, except with recombinant rat interferon gamma where the time interval was 3 h. Endotoxin significantly reduced basal and sodium taurocholate-stimulated bile flow, as well as sodium taurocholate secretion. No such effect was noted after acute administration of any of these lymphokines or chronic administration of interleukin-1. The cholestasis induced by endotoxin administration is not mediated by interleukin-1, interleukin-2 or recombinant interferon gamma.
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PMID:Lymphokines and bile secretion in the rat. 295 76

Impaired immune competence leading to decreased resistance to sepsis is a major cause of death in burn patients. We have previously shown that increased mortality from a septic challenge correlated with impaired splenocyte interleukin-2 (IL-2) production and response to T cell mitogens in mice subjected to a 25% surface area scald burn. We report now that the addition of recombinant (r) IL-2 (100 U/ml) in vitro to splenocytes from burned animals restored mitogen responses to normal. Burned mice intraperitoneally received 16,000 U of rIL-2 (selected on the basis of dose-response experiments) once daily in 0.5 ml 5% dextrose (5% D) on days 1 through 6 after thermal injury and were compared with burned mice treated with only 5% D. Both groups were subjected to cecal ligation and puncture 10 days after burn; 4 days later, there were no survivors in the 5% D group, whereas 45% of the rIL-2 group remained alive (p = 0.001; Gehan statistic). We found that rIL-2 treatment at the dose selected resulted in no apparent toxicity in burned mice. Finally, splenocytes from rIL-2-treated burned mice showed improved responses to T cell mitogens in vitro compared with 5% D-treated controls. We conclude that rIL-2 therapy may have a role in the restoration of immune competence after thermal injury.
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PMID:Recombinant interleukin-2 (rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice. 326 Oct 49

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


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