Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004610 (bacteremia)
 13,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chest roentgenograms of 54 patients receiving high dose interleukin-2 with or without lymphokine-activated killer cell therapy for advanced cancer were retrospectively reviewed. Thirty-nine patients (72 percent) developed chest roentgenographic abnormalities consisting of pleural effusions, 28 (52 percent); diffuse infiltrates (pulmonary edema), 22 (41 percent); and focal infiltrates, 12 (22 percent). These abnormalities resolved in 30 of 39 (77 percent) patients by four weeks after therapy. Simple pleural effusions were the only residual roentgenographic abnormalities seen and were present primarily in patients receiving IL-2 by bolus intravenous injection (8 of 28) (29 percent) as compared to continuous intravenous infusion (1 of 24) (4 percent) (p = 0.03). Only roentgenographic evidence of pulmonary edema appeared to correlate with the degree of clinical pulmonary toxicity (p = 0.001). The development of chest roentgenographic abnormalities correlated with the administration of IL-2 solely by bolus intravenous injection (p = 0.04), a pretreatment FEV1 of less than 3 L (p = 0.04), and treatment associated bacteremia (p = 0.09), but not with prior therapy, the presence of pulmonary metastases or the degree of systemic capillary leak as measured by percentage of weight gain during therapy. Although the roentgenographic abnormalities did not relate to the number of LAK cells received, two patients developed sudden onset of dyspnea and chest roentgenographic evidence of pulmonary edema shortly after the first LAK cell administration, implying that a direct cause-and-effect relationship exists in some patients. Possible mechanisms for these IL-2 related chest roentgenographic abnormalities and pulmonary toxicity in general are discussed.
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PMID:Chest roentgenographic abnormalities in IL-2 recipients. Incidence and correlation with clinical parameters. 154 Nov 42

Mycobacterium avium complex (MAC) is the most common bloodstream pathogen isolated from patients with AIDS. We have previously shown that TNF alone or in combination with IL-2 can activate human and murine macrophages in vitro to kill MAC strains isolated from disseminated infections. To determine whether treatment with TNF and IL-2 could effect the course of disseminated MAC infections in a murine model of disseminated MAC infection, we infected C57BL mice with 3 x 10(8) bacteria i.v. and 1 wk later administered: 1) IL-2, 100 micrograms/kg; 2) TNF, 25 micrograms/kg; 3) IL-2, 50 micrograms/kg, and TNF, 12.5 micrograms/kg; and 4) saline. IL-2 was injected i.p. daily with TNF being administered in cycles of 3 out of 4 consecutive days. Fourteen days after starting therapy, blood was cultured and mice were sacrificed for quantitative cultures of liver and spleen homogenates. IL-2, TNF, and IL-2/TNF treated groups showed an 87 +/- 5%, 57 +/- 9%, 88 +/- 6% decrease in bacteremia (p = 0.05 for TNF-treated animals and less than 0.04 for the other two groups, compared with control). The combination IL-2/TNF was the only treatment that showed a trend toward an absolute decrease in the number of bacteria in the blood. Reduction in colony counts of liver and spleen were 77 +/- 4% and 87 +/- 6%, respectively, for treatment with IL-2, 58 +/- 7% and 87 +/- 5% for TNF, and 60 +/- 10% and 82 +/- 6% for IL-2/TNF, respectively. These results suggest that both cytokines may play a role in the control of Mycobacterium avium infection and that the combination of a half-dose of IL-2 and TNF, despite not showing any greater efficacy, can be less toxic than TNF or IL-2 alone and might be useful for the therapy of disseminated infection.
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PMID:Treatment of experimental disseminated Mycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor. 255 16

Excessive cytokine expression induced by superantigen may be one aspect of the pathophysiology associated with Gram positive bacteremia. We have undertaken a study of the kinetics of cytokine production in lymph nodes obtained from in vivo Staphylococcus enterotoxin B (SEB) treated animals. This study was designed to evaluate the short term cytokine profile observed using immunohistochemistry (IHC) in BALB/c mice injected intraperitoneally (i.p.). The observed immunohistochemical kinetic profiles were corroborated using reverse transcription-polymerase chain reaction (RT-PCR) RNA analysis. We report here that TNF, IL-2, and IFN-gamma are the principal cytokines which were detected within hours of SEB administration, and that other cytokines such as IL-3, IL-4, IL-5, IL-6, IL-10, GM-CSF and M-CSF were undetectable. TNF and IL-2 appeared very early following SEB priming, and were observed by 1 h. IFN-gamma which appeared later (maximally at 14 h) was produced predominantly by CD8+ cells. In contrast, the TNF and IL-2 were produced primarily by CD4+ cells. Identical results were obtained by IHC and RT-PCR; the kinetics of mRNA expression slightly preceded the appearance of protein. The TNF and IFN-gamma staining patterns observed in lymph node sections were indicative of Golgi-localized cytokine. The IL-2 staining pattern observed in lymph node sections was distinctive, covering a significant local area of cells. This local regional concentration of IL-2, which may result from cytokine attached to extracellular binding components, may be an important aspect of the activation phase of a developing immune response. Rapid induction and excessive cytokine production elicited by superantigen in vivo, may ultimately help to explain the shock and death associated with SEB.
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PMID:Early expression of cytokines in lymph nodes after treatment in vivo with Staphylococcus enterotoxin B. 793 Jun 39

Patients undergoing immunotherapy with interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed that a profound deficiency of neutrophil chemotaxis is induced by interleukin-2 therapy. Migration in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), being normal before therapy, was markedly impaired after the first cycle and further decreased after the third cycle of treatment. A direct effect of interleukin-2 on neutrophil chemotaxis is controversial. However, peripheral blood cells exposed to interleukin-2 secrete secondary cytokines. In particular, the release of tumor necrosis factor after interleukin-2 injection has been proposed as an important regulatory mechanisms. When testing random migration and chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients, we found that this serum induced a defective chemotaxis similar to that of neutrophils from interleukin-2-treated patients. In order to assess the influence of tumor necrosis factor, we tested the effect of anti-tumor necrosis factor-alpha antibody on the chemotactic response of cells after incubation with the serum, and we observed a dose-dependent reduction of neutrophil chemotaxis deficiency. These data suggest that TNF is counteracting the neutrophil chemotactic deficiency observed during IL-2 treatment.
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PMID:In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor. 834 39

A burned rabbit's model (20% TBSA) was used in this study. The sera taken from the burned rabbits without bacteremia and sepsis showed immune suppressive effects, especially the sera obtained 4 days after injury. After being separated by ultrafiltration, the burned sera were divided into three groups. The ultrafiltrating substances with molecular weight below 10 Kd or between 10 to 30 Kd were found to reduce the production of IL-2 and the lymphocyte blastogensis stimulated by Con A. The substances with molecular weight greater than 30 Kd also showed profound immune suppressive action on lymphocyte. No obviously abnormal protein was found in the burned serum analysed with SDS electrophoresis. It is concluded that the immune suppressive substances in the burned serum were characterised by complexity in components and a wide range of molecular weight.
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PMID:[A study of immune suppression activity of serum from burned rabbits]. 920 60

The current studies demonstrate protective and harmful effects of neutrophils (PMN) during experimental sepsis after cecal ligation and puncture (CLP). It is known that CLP induces signaling defects in blood PMN. When PMN were depleted 12 h after CLP, there were dramatic reductions in levels of bacteremia, evidence for reduced liver and renal dysfunction, sharp reductions in serum levels of cytokines (IL-1beta, IL-6, IL-10, TNF-alpha, and IL-2), and improved survival. In contrast, PMN depletion before CLP resulted in substantial increases in bacteremia and no evidence for attenuation of liver and renal failure dysfunction. These data suggest that at the onset of sepsis, PMN are important in regulating the levels of bacteremia, whereas after the onset of sepsis, as they lose innate immune functions, their presence is associated with higher levels of bacteremia and intensified organ dysfunction.
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PMID:Harmful and protective roles of neutrophils in sepsis. 1598 19

Bacterial translocation (BT) is defined as the passage of indigenous bacteria colonizing the intestine through the epithelial mucosa to the mesenteric lymph nodes and other sites. It can even cause the development of lethal sepsis. BT is being studied extensively, most research being conducted on animal, mostly murine, models. The cause of BT is not well known. Despite advances in antimicrobial therapy, the mortality rate associated with bacteremia is still high, and sepsis can often originate from the patient's own intestinal flora. Consequently, a better understanding of the mechanisms of BT as well as mechanisms operating to prevent bacteria from translocating from the gastrointestinal tract may provide more logical treatment of particular patients. BT may be promoted by immunosuppression (probably one of the most important factors causing the increase in BT), disturbances in the normal ecology of the gastrointestinal tract, allowing some indigenous bacteria to overgrow others, and by mucosal injuries. This article discusses the potential role of various factors responsible for BT and the relationship between BT and neoplastic disease. It also emphasizes the significance of the immune system, which appears to play a role in the ontogeny of gut-associated lymphoid tissue (GALT), including the role of IL-2 (which induces an increase in BT) and the macrophage, which participates in the transport of bacteria from the intestinal lumen to mesenteric lymph nodes. A better understanding of the immunopathology of BT may contribute to the development of novel means of therapy for sepsis and other serious complications of bacterial infection.
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PMID:[Bacterial translocation and its clinical significance]. 1599 93

Apoptosis of CD4(+) T cells and T(H)2 polarization are hallmarks of sepsis-induced immunoparalysis. In this study, we characterized sepsis-induced adaptive immune dysfunction and examined whether improving T-cell effector function can improve outcome to sepsis. We found that septic mice produced less antigen-specific T-cell-dependent IgM and IgG(2a) antibodies than sham-treated mice. As early as 24 hours after sepsis, CD4(+) T cells proliferated poorly to T-cell receptor stimulation, despite normal responses to phorbol myristate acetate and ionomycin, and possessed decreased levels of CD3zeta. Five days following immunization, CD4(+) T cells from septic mice displayed decreased antigen-specific proliferation and production of IL-2 and IFN-gamma but showed no difference in IL-4, IL-5, or IL-10 production. Treatment of mice with anti-GITR agonistic antibody restored CD4(+) T-cell proliferation, increased T(H)1 and T(H)2 cytokine production, partially prevented CD3zeta down-regulation, decreased bacteremia, and increased sepsis survival. Depletion of CD4(+) T cells but not CD25(+) regulatory T cells eliminated the survival benefit of anti-GITR treatment. These results indicate that CD4(+) T-cell dysfunction is a key component of sepsis and that improving T-cell effector function may be protective against sepsis-associated immunoparalysis.
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PMID:Treatment with GITR agonistic antibody corrects adaptive immune dysfunction in sepsis. 1769 Feb 55

Methicillin-resistant Staphylococcus aureus (MRSA) infection remains a serious hazard to global health. The use of immune modulatory therapy to combat infection is gaining an interest as a novel treatment alternative. Lactoferrin (LF), an iron binding protein with immune modulating properties, has the potential to modify the course of systemic MRSA infection. Specifically, LF is capable of limiting deleterious inflammatory responses while promoting the development of antigen specific T-cell activity. The efficacy of a novel recombinant mouse LF (rmLF) to protect against MRSA infection was examined in a mouse peritonitis model. BALB/c mice were infected with a lethal dose of MRSA and treated at 2h post-infection with rmLF. Effects of rmLF on MRSA-infected primary monocytes and granulocytes were analyzed for inflammatory mediators. The rmLF treated mice demonstrated a modest increase in survival of more than 24h, albeit with reduced bacteremia. Serum cytokines, IL-17 and IL-6, were significantly reduced post-challenge post-rmLF treatment. The rmLF led to a minor decrease in IL-1b, and a slight increase in TNF-a production. Preliminary investigation towards human clinical relevance was accomplished using human blood derived monocytes and granulocytes infected with MRSA and treated with homologous recombinant human LF (rhLF). Treatment with (rhLF) led to increased production of IFN-g and IL-2. The human cell studies also showed a concurrent decrease in TNF-a, IL-6, IL-1b, IL-12p40, and IL-10. These results indicate that the rmLF and rhLF have a high degree of overlap to modify inflammatory responses, although differences in activities were observed between the two heterologous recombinant molecules.
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PMID:Immunomodulatory effects of recombinant lactoferrin during MRSA infection. 2461 6

Infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death in human immunodeficiency virus (HIV)+ individuals, particularly in Sub-Saharan Africa. Management of this deadly co-infection is a significant global health challenge that is exacerbated by the lack of efficient vaccines against both Mtb and HIV, as well as the lack of reliable and robust animal models for Mtb/HIV co-infection. Here we describe a tractable and reproducible mouse model to study the reactivation dynamics of latent Mtb infection following the loss of CD4+ T cells as it occurs in HIV-co-infected individuals. Whereas intradermally (i.d.) infected C57BL/6 mice contained Mtb within the local draining lymph nodes, depletion of CD4+ cells led to progressive systemic spread of the bacteria and induction of lung pathology. To interrogate whether reactivation of Mtb after CD4+ T cell depletion can be reversed, we employed interleukin (IL)-2/anti-IL-2 complex-mediated cell boost approaches. Although populations of non-CD4 lymphocytes, such as CD8+ memory T cells, natural killer (NK) cells and double-negative (DN) T cells significantly expanded after IL-2/anti-IL-2 complex treatment, progressive development of bacteremia and pathologic lung alterations could not be prevented. These data suggest that the failure to reverse Mtb reactivation is likely not due to anergy of the expanded cell subsets and rather indicates a limited potential for IL-2-complex-based therapies in the management of Mtb/HIV co-infection.
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PMID:A Mouse Model of Latent Tuberculosis Infection to Study Intervention Strategies to Prevent Reactivation. 2739 Oct 12


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