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

Sepsis remains a major risk in the high mortality and morbidity after surgery for obstructive jaundice. The reasons for the increased susceptibility to infection are unknown. This study examined interleukin 2 (IL-2) production and the lymphocyte response to PHA mitogen in 31 patients with obstructive jaundice. Among them, 18 patients were simultaneously investigated by enumeration of T lymphocyte subsets in peripheral blood with APAAP technique. The results showed that the patients had significantly decreased IL-2 production and lymphocyte response to PHA mitogen. The percentage of Leu 3a (helper/inducer T cell) in the patients was significantly lower than that in normal controls. Leu 3a/Leu 2a (suppressor/cytotoxic T cell) ratio was significantly lower in these patients. The reduction of IL-2 production correlated significantly with the suppression of lymphocyte proliferation but not with the percentage of Leu 3a cells. From these results, it may be suggested that the reduction of IL-2 production in the patients with obstructive jaundice is an important reason for the suppression of T lymphocyte proliferative response, not merely a reflection of the decrease of helper T cells.
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PMID:Interleukin 2 production and its relationship with T lymphocyte subsets in patients with obstructive jaundice. 145 6

A murine model of experimental sepsis, ie, cecal ligation and puncture, was used to determine the potential effects of infection on in vitro cell-mediated immunity. Following cecal ligation and puncture, in vitro responses of mouse splenocytes to mitogens (phytohemagglutinin and concanavalin A), the effects of in vitro interleukin 2 on these responses, and the impact of in vivo interleukin 2 on survival were studied. Compared with controls (sham cecal ligation and puncture), phytohemagglutinin responses 1 day after cecal ligation and puncture were enhanced (43% +/- 17%, n = 9), phytohemagglutinin and concanavalin A responses at day 4 were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%), and, by day 7, phytohemagglutinin and concanavalin A responses were approaching values in mice treated by sham cecal ligation and puncture. Suppressed phytohemagglutinin responses at day 4 after cecal ligation and puncture were restored to normal with in vitro interleukin 2 (61,052 +/- 3407 cpm for cecal ligation and puncture and 64,643 +/- 4727 cpm for sham cecal ligation and puncture). Mortalities following cecal ligation and puncture were identical at day 1 after cecal ligation and puncture (6/20) for both interleukin 2- and vehicle-treated groups; thereafter, interleukin 2-treated groups fared better. At day 1 after cecal ligation and puncture, the mean spleen cell phytohemagglutinin response was enhanced (43.8% +/- 17%, n = 9) compared with sham cecal ligation and puncture (= 10). By day 4, the responses to both concanavalin A and phytohemagglutinin were suppressed (45.5% +/- 4.4% and 57.5% +/- 5.6%, respectively). Responses at day 7 approached those of controls given sham cecal ligation and puncture. Sepsis causing a temporary impairment of cell-mediated immunity may be a factor in the frequent coexistence of altered cell-mediated immunity and sepsis, and interleukin 2 may have a role in limiting the adverse effects of sepsis.
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PMID:Impaired cell-mediated immunity in experimental abdominal sepsis and the effect of interleukin 2. 152 87

Hemorrhagic shock causes a severe suppression of cellular immunity and an increased susceptibility to sepsis that may be due to increased release of prostaglandin E2 by macrophages. Since chloroquine inhibits the secretion of prostaglandin E2 by macrophages in vitro, the effects of chloroquine administration in vivo following hemorrhagic shock on macrophage prostaglandin E2 secretion and on depressed cellular immunity were examined. Inbred C3H/HeN male mice, aged 6 to 8 weeks, were bled to a mean blood pressure of 35 mm Hg, which was maintained for 60 minutes, and adequately, resuscitated. Mice then received intramuscular injections of either saline (vehicle) or chloroquine (10 mg/kg of body weight). Prostaglandin E2 in macrophage supernatants (radioimmunoassay) concanavalin A-dependent splenocyte proliferation, and interleukin 2 in splenocyte supernatants (CTLL 20 interleukin 2-dependent proliferation) were determined 2 or 24 hours later. Hemorrhage caused a significant decrease of splenocyte proliferation (47%) and interleukin 2 release (49%) at 24 hours, while prostaglandin E2 secretion from macrophages was elevated at 2 hours. Chloroquine treatment attenuated depression of splenocyte functions and reduced prostaglandin E2 release. Furthermore, chloroquine treatment decreased the mortality of septic mice after hemorrhage to levels comparable with those of sham-operated mice. Thus, chloroquine may be a useful adjunct in the clinical setting for the treatment of shock-induced immunodepression and increased susceptibility to sepsis following hemorrhage.
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PMID:Chloroquine attenuates hemorrhagic shock-induced immunosuppression and decreases susceptibility to sepsis. 173 52

Traumatic injury often results in profound immunopathology that can lead to immunosuppression, thereby increasing the morbidity and mortality due to sepsis. The isolation and partial characterization of an immunosuppressive glycopeptide (SAP) from serum of severely burned patients has previously been reported by our laboratory. Recently, this trauma peptide has also been identified in the serum of patients with multiple blunt trauma. This glycopeptide is capable of suppressing neutrophil chemotaxis, T-cell blastogenesis and the lysis of human erythrocytes. We demonstrate in this report that SAP inhibits interleukin 2 (IL-2) biosynthesis by mitogen-stimulated peripheral blood mononuclear cells. Peptide concentrations of 50 nmol and above significantly inhibited IL-2 production. Inhibition was not reduced by the addition of indomethacin or anti-PGE2 to cultures containing greater than 100 nmol of peptide, suggesting that inhibition is not entirely prostaglandin-mediated. Preliminary studies have shown that IL-2 suppression by SAP can be partially reversed by the addition of calcium ionophore. These results suggest a potential immunosuppressive mechanism of the trauma peptide in which T cell blastogenesis is inhibited by interference in IL-2 biosynthesis.
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PMID:In vitro inhibition of IL-2 biosynthesis in activated human peripheral blood mononuclear cells by a trauma-induced glycopeptide. 210 88

Sepsis remains the major cause of postresuscitation death after hemorrhage and trauma. The high incidence of infection in this setting has been attributed to host defense abnormalities, including dysfunction in cell-mediated immunity. To elucidate the interaction between injury and host defense mechanisms, we measured interleukin 2 (IL 2) production by peripheral blood mononuclear cells in 21 patients immediately after unanesthetized, accidental hemorrhage or trauma. Interleukin 2 production in minimally injured patients (0.63 +/- 0.14 [SEM] units) was similar to that found in control, uninjured subjects (0.68 +/- 0.17 units). Compared with control patients, IL 2 production was reduced 56% in patients with moderate injury and 85% in patients with severe injury. There was significant correlation between the severity of injury and the reduction in IL 2 production. Lymphocyte proliferative response to phytohemagglutinin was reduced in patients with moderate and severe injury, and the reduction in proliferative response was significantly correlated with injury severity. These results indicate that marked abnormalities in cell-mediated immune function, as determined by IL 2 production, occur immediately after hemorrhage and accidental injury.
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PMID:The effects of hemorrhage and trauma on interleukin 2 production. 387 97

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) (n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli occurred in all rats treated with 10(5) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics and occasional mucosal disruption was seen only in the group receiving 10(5) IU. These data show that rIL-2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.
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PMID:High-dose interleukin 2 promotes bacterial translocation from the gut. 766 73

Sepsis is a major factor in the high mortality and morbidity following diagnostic and therapeutic procedures in patients with obstructive jaundice. The reasons for this increased susceptibility to infection are not fully understood. We therefore observed prospectively changes in immunological status of patients with obstructive jaundice in the perioperative period and studied immunological effects of perioperative arginine therapy. The results showed that there was a significant reduction in interleukin 2 (IL-2) production, interleukin 2 receptor (IL-2R) expression and lymphocyte response to phytohemagglutinin (PHA) mitogen in patients with obstructive jaundice compared with normal controls. After operation, the immune suppression in patients with obstructive jaundice was more significant. Arginine is a known T lymphocyte stimulator. Perioperative supplement with arginine significantly enhanced the immune function of patients with obstructive jaundice, the mechanism being related to increased IL-2 production and IL-2R expression.
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PMID:Immunological status of patients with obstructive jaundice and immunostimulatory effect of arginine. 823 Mar 55

Studies have suggested that the significant suppression of cellular immunity following hemorrhage may be due to an increased release of prostaglandin E2 (PGE2) by macrophages. Since diets high in n-3 polyunsaturated fatty acids decrease PGE2 synthesis, we assessed whether hemorrhage-induced immunosuppression could be prevented by dietary manipulation. C3H/HeN mice were fed for 3 weeks with fat sources derived from corn oil, safflower oil, or fish oil, then bled to a mean blood pressure of 35 mm Hg maintained for 60 minutes. Following this, the animals were adequately resuscitated with fluids and killed 24 hours later. In the corn oil and safflower oil groups, hemorrhage resulted in a significant increase in PGE2 release by peritoneal macrophages, a marked suppression of peritoneal macrophage antigen presentation capacity, interleukin 1 release, splenocyte proliferation, and interleukin 2 secretion compared with shams. However, feeding mice with fish oil for 3 weeks prior to hemorrhage prevented the rise in PGE2 release and maintained normal macrophage and splenocyte functions following hemorrhage. Thus, the elevated release of PGE2 by peritoneal macrophages plays a pivotal role in hemorrhage-induced immunosuppression. Moreover, diets high in n-3 polyunsaturated fatty acids may offer a new therapeutic approach for preventing posthemorrhage immunosuppression and increased mortality from sepsis.
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PMID:Modulation of macrophage membrane phospholipids by n-3 polyunsaturated fatty acids increases interleukin 1 release and prevents suppression of cellular immunity following hemorrhagic shock. 841 75

Critical illness is associated with both immunosuppression and glutathione deficiency. We determined if in vivo depletion of glutathione would adversely affect immune status. Rats with normal glutathione levels and those with glutathione stores depleted by diethyl maleate underwent analysis of splenocyte function and mesenteric lymph node lymphocyte function. Lymphocytes of the spleen and mesenteric lymph nodes were tested for concanavalin A proliferative response and interleukin 2 production. Tumor necrosis factor and interleukin 6 secretion by splenic adherent cells was also measured. Glutathione-depleted animals had significantly decreased lymphocyte proliferation and decreased production of tumor necrosis factor and interleukin 6 but unaltered interleukin 2 production. These findings indicate that in vivo glutathione deficiency impairs macrophage and T-cell function. Because glutathione depletion may occur in sepsis, trauma, and shock, treatments that help maintain glutathione levels may enhance immunocompetence and thus improve the ability of patients to recover from critical illness.
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PMID:Glutathione depletion in rats impairs T-cell and macrophage immune function. 841 77

We examined whether (1) there is an association between elevated circulating levels of transforming growth factor-beta (TGF-beta) and splenocyte dysfunction during sepsis, and (2) administration of monoclonal antibodies to interleukin 6 (an inducer of TGF-beta release) or TGF-beta could ablate these changes. Blood and splenocytes were obtained from C3H/HeN mice at 1, 4, or 24 hours following cecal ligation and puncture or sham operation. Only at 24 hours after cecal ligation and puncture was there an association between elevated blood TGF-beta value and depressed splenocyte interleukin 2 release. Administration of monoclonal antibodies against interleukin 6, but not against TGF-beta (intraperitoneally immediately following cecal ligation and puncture), significantly decreased the blood levels of TGF-beta at 24 hours following cecal ligation and puncture and improved splenocyte interleukin 2 release. Thus, the judicious use of monoclonal antibodies against interleukin 6 may block the subsequent elevation of TGF-beta, thereby attenuating host immunosuppression during sepsis.
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PMID:Role of interleukin 6 and transforming growth factor-beta in the induction of depressed splenocyte responses following sepsis. 841 86


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