Tumor necrosis factor, interleukin-6,and epinephrine are associated with hypermetabolism in AIDS patients with acute opportunistic infections.

During a 9-day period we investigated body composition, resting energy expenditure (REE), IL-6, TNF, and sTNFR-55 and sTNFR-75 plasma concentrations during infectious complications in 12 patients with HIV disease. At study entry, IL-6 was detectable in 5 and TNF in 10 patients. TNF was closely correlated with sTNFR-75 concentration (r = 0.

Animal pharmacokinetics of the tumor necrosis factor receptor-immunoglobulin fusion protein lenercept and their extrapolation to humans.

The pharmacokinetics of the tumor necrosis factor receptorimmunoglobulin fusion protein, lenercept, were assessed in rats, rabbits, dogs and cynomolgus monkeys. Pharmacokinetic parameters were extrapolated to humans by allometric scaling. Lenercept was dosed i.

Increased serum levels of soluble tumor necrosis factor a-receptors in patients undergoing partial liver resection.

Background/aims: This study was conducted to evaluate the association of tumor necrosis factor-a and soluble receptors as known antagonists in liver surgery with regard to ischemia and reperfusion.

Methodology: Preoperative and perioperative changes of TNF, soluble TNF receptor I and II as well as IL-6 were evaluated in twelve patients with partial liver resection. Before liver ischemia and after reperfusion, the levels were measured in the portal and hepatic vein, as well as systemically.

Th1 and Th2 cytokine response patterns in leukocyte cultures of patients with urinary bladder, renal cell and prostate carcinomas.

As a decreased production of Th1 cytokines by stimulated peripheral blood leukocytes has recently been shown in patients with various carcinomas, the present study was performed to determine whether these patients also exhibit a Th1/Th2 imbalance compared to healthy controls. We measured the production of the Th1 cytokines IL-2 and IFN-gamma as well as the Th2 cytokines IL-4, IL-6 and IL-10 in mitogen-stimulated peripheral blood mononuclear cell (PBMC) cultures of patients with urinary bladder carcinomas (n = 47), prostate carcinomas (n = 111) and renal cell carcinomas (n = 67) as compared to 40 age-matched healthy controls. In the PBMC cultures of the tumor patients, the levels of the Th1 cytokines IL-2 and IFN-gamma were lower as compared to the controls.

Serum levels of p55 and p75 soluble TNF receptors in adult acute leukaemia at diagnosis: correlation with clinical and biological features and outcome.

The tumour necrosis factor (TNF)/TNF-receptor (TNFR) complex plays a role in the growth of leukaemic cells. We retrospectively investigated the relationship between pretreatment serum concentration of soluble TNFR (p55- and p75-sTNFRs) and outcome in adult acute myeloid (AML 82 cases) and lymphoid (ALL 44 cases) leukaemia. Both sTNFRs were significantly higher in AML (p55-sTNFR 4.

Bile duct epithelia as target cells in primary biliary cirrhosis and primary sclerosing cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic autoimmune-mediated diseases of the biliary tree, resulting in a loss of bile ducts. There are morphological features that clearly distinguish them from each other: in PBC, there is overt destruction of the bile ducts with disruption of the basement membrane; in PSC there is abundant periductular fibrosis with shrinkage and subsequent loss of the bile ducts. In order to see if the disparate histopathology is paralleled by different immunohistology we looked at a panel of epitopes on bile duct epithelia especially to see if biliary epithelial cells may present as targets for cell mediated immune response.

Cytokines, nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: comparisons in patients with septic shock, cardiogenic shock, and bacterial pneumonia.

Objectives: To determine and compare the respective concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, soluble TNF receptors, nitrite/nitrate (NO2-/NO3-), and procalcitonin in the plasma of patients with septic shock, cardiogenic shock, and bacterial pneumonia without shock; and to assess the predictive value of these mediators in defining patients with septic shock.

Design: Cohort study, comparing normal volunteers (controls) and patients with septic shock, cardiogenic shock, and bacterial pneumonia.

Setting: A collaborative study among an intensive care unit, an emergency room, and three research laboratories.

Systemic levels of the T cell regulatory cytokines IL-10 and IL-12 in Bechçet's disease; soluble TNFR-75 as a biological marker of disease activity.

Objective: To analyze the levels of the T cell regulatory cytokines interleukin 10 (IL-10) and IL-12 in plasma of patients with Behçet's disease (BD), and to assess the value of cytokines and cytokine antagonists as biological markers of disease activity.

Methods: Sera/plasma of 66 consecutive outpatients with established diagnosis of BD were analyzed for the presence of IL-2R, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble (s) TNF receptor (R)-55, sTNFR-75, IL-10, and IL-12 using immunological methods. Additional laboratory measurements included erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).

Serum levels and in situ expression of TNF-alpha and TNF-alpha binding proteins in inflammatory liver diseases.

Cells respond to tumour necrosis factor-alpha (TNF-alpha) via binding to 75-kDa (type A) and 55-kDa (type B) receptors which have different intracellular signalling pathways and can also circulate as soluble molecules. Both receptors are co-expressed in many tissues, but their relative contributions to cellular TNF responses is for most situations unknown. In patients with viral and non-viral inflammatory liver diseases serum TNF-alpha was determined by an immunoenzymetric assay and soluble type A and B TNF receptors (TNF-alpha r) by enzyme-linked immunological and biological assays (ELIBA).

Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection.

Objective: To evaluate plasma levels of interleukin-6 (IL-6) and soluble tumor necrosis factor receptors (sTNF-R) 55 and 75 in neonates as a contribution to the early diagnosis of infection.

Study Design: We prospectively measured IL-6 and sTNF-R 55 and sTNF-R 75 plasma levels in 157 newborn infants admitted to our regional neonatal center in a 3-month period and in cord blood of 131 newborn infants delivered in our obstetrics unit. C-reactive protein was sequentially determined after admission.

Interleukin 1 (IL-1) receptor antagonist, soluble tumor necrosis factor receptors, IL-1 beta, and IL-8--markers of remission in rheumatoid arthritis during treatment with methotrexate.

Objective: To examine circulating levels of cytokines and cytokine inhibitors and their production by blood mononuclear cells (MNC) in patients with active rheumatoid arthritis (RA) before treatment with methotrexate (MTX) and inactive disease upon treatment as well as healthy control individuals.

Methods: Interleukin-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptors p55 and p75 (sTNFr; p55 and p75), interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and monocyte chemoattractant protein 1 (MCP-1) were assessed by immunoassays in sera and MNC culture supernatants of 27 patients with RA with active disease before and 14 patients with inactive disease during MTX treatment, and 10 healthy controls.

Results: Levels of circulating IL-1ra, sTNFr p55 and p75 were higher in patients with active RA compared to those with inactive disease or controls.

Anti-interferon-gamma antibodies in a patient undergoing interferon-gamma treatment for systemic mastocytosis.

An 81-year-old woman with systemic mastocytosis responded to subcutaneous recombinant interferon-gamma (rIFN-gamma) treatment for about 6 months, when intestinal symptoms gradually recurred. A serum sample obtained 3 months later was positive for specific rIFN-gamma-binding antibodies, which had been absent at the initiation of treatment. Cessation of IFN-gamma therapy was followed by a slow decline of IFN antibody titers.

Different pattern of local and systemic release of proinflammatory and anti-inflammatory mediators in severely injured patients with chest trauma.

Background: Excessive release of proinflammatory cytokines has been involved in pathogenesis of acute respiratory distress syndrome.

Design: Since injured patients with chest trauma reveal a high risk for posttraumatic acute respiratory distress syndrome, local and systemic release of proinflammatory cytokines and their naturally occurring inhibitors were determined in the early posttraumatic period.

Materials And Methods: Proinflammatory and anti-inflammatory mediators were measured in plasma and bronchoalveolar lavage fluid (BALF) from 16 patients with multiple injuries including severe chest injury (Injury Severity Score of 34.

Weight gain and increased concentrations of receptor proteins for tumor necrosis factor after patients with symptomatic HIV infection received fortified nutrition support.

Objective: To determine whether certain nutrients and dietary factors act as modulators of the immune system and improve the nutritional status of immunocompromised patients.

Design: Controlled, double-blind, crossover phase trials of the effects of a fortified formula in patients infected with the human immunodeficiency virus (HIV). Patients consumed a control formula for 4 months and a study formula for 4 months.

Protection against lethal Escherichia coli bacteremia in baboons (Papio anubis) by pretreatment with a 55-kDa TNF receptor (CD120a)-Ig fusion protein, Ro 45-2081.

Fusion proteins of the human 55-kDa TNF receptor extracellular domain with hinge and C2/C3 constant domains of human IgG1 or IgG3 heavy chains were tested in a primate sepsis model. Twenty-four baboons received 4.6, or 0.

Nitric oxide-independent inhibitory effects of L-arginine analog NG-monomethy-L-arginine on the generation of interleukin-2 activated cytotoxic activity in humans.

Nitric oxide (NO) derived intracellularly from L-arginine (Arg) is indispensable for optimalgeneration of lymphokine-activated killer (LAK) cell activity in rodents. Still unclear, however, is its role in humans. To address this question human peripheral blood mononuclear cells (PBMC) from healthy donors were cultured in L-arginine free medium supplemented with recombinant interleukin-2 (rIL-2) and in the presence of exogenous L-arginine analog NG-monomethyl-L-arginine (NMMA), a specific inhibitor of the NO synthetic pathway.

Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV-seronegative patients with Pneumocystis carinii pneumonia.

Concentrations and ex vivo production of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1RA) and TNF soluble receptors were followed in bronchoalveolar lavage (BAL) fluid and blood from 10 HIV-seronegative patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy volunteers. During the acute phase of PCP, TNF but not IL-6 or IL-1beta was detectable in BAL fluid. At that time, plasma concentrations of the proinflammatory cytokines were low, whereas plasma concentrations of the anti-inflammatory cytokines were high.

Analysis of the immune reactivity of infiltrating and peripheral lymphocytes from patients with renal cell carcinoma by measuring cytokine secretion.

The immunological properties of tumour-infiltrating (TIL) and peripheral blood lymphocytes (PBL) from 29 patients with renal cell carcinomas were characterized with respect to their phenotypic expression and cytokine production. TIL were isolated from mechanically disaggregated tumor material and PBL from peripheral blood by gradient centrifugation. To eliminate all non-lymphoid cells, CD3-positive cells were specifically separated from these cell fractions with anti-CD3 magnetic beads.

Cytokine production in leukocyte cultures during therapy with Echinacea extract.

We measured the levels of the cytokines IL-1-alpha, IL-1-beta, IL-2, IL-6, TNF-alpha, and IFN-gamma in culture supernatants of stimulated whole blood cells derived from 23 tumor patients undergoing a 4-week oral treatment with a spagyric extract from Echinacea angustifolia, Eupatorium perfoliatum, and Thuja occidentalis (Echinacea complex). All patients had had curative surgery for a localized solid malignant tumor. Blood was taken before treatment and after 2 and 4 weeks of therapy.

Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM.

To determine whether cytokines could have a role in the development of insulin-dependent diabetes mellitus (IDDM), we measured serum levels of cytokines derived from T helper 1 (interleukin-2 and interferon-gamma), T helper 2 (interleukin-4 and interleukin-10) lymphocytes and macrophages (tumour necrosis factor-alpha, interleukin-1 alpha and interleukin-1 beta) in patients before and after the onset of IDDM. Recently diagnosed IDDM patients had significantly higher levels of interleukin-2, interferon-gamma, tumour necrosis factor-alpha and interleukin-1 alpha than patients with either long-standing IDDM, non-insulin-dependent diabetes (NIDDM), Graves' disease, or control subjects (p < 0.05 for all).

Peripheral natural killer cell activity and intraperitoneal soluble p55 tumor necrosis factor receptor in patients with malignant ascites: two possible indicators for response to intraperitoneal combined tumor necrosis factor alpha and interferon gamma treatment.

Tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) are important immunomodulators. They are capable of acting in a synergistic manner on tumor cells in vitro and in vivo. In a clinical phase I study 13 patients with malignant ascites due to abdominal spread of different primary tumors received intraperitoneally (i.

Selective suppression of cytokine secretion in patients with small-cell lung cancer.

Background: Whether or not cytokine secretion is impaired in patients with small-cell lung cancer (SCLC), is unknown. We therefore investigated whether cytokine secretion by immunocompetent cells may be suppressed in patients with SCLC.

Patients And Methods: We determined cytokine secretion by lymphocytes and monocytes in whole blood cell cultures from 58 patients with SCLC, 95 patients with non-small-cell lung cancer (NSCLC), 10 patients with nonmalignant lung disease and from 44 normal healthy individuals by using an enzyme-linked immunosorbent assay (ELISA) specific for the different cytokines measured.

Effect of cell cycle on the regulation of the cell surface and secreted forms of type I and type II human tumor necrosis factor receptors.

The cell cycle has been shown to regulate the biological effects of human tumor necrosis factor (TNF), but to what extent that regulation is due to the modulation of TNF receptors is not clear. In the present report we investigated the effect of the cell cycle on the expression of surface and soluble TNF receptors in human histiocytic lymphoma U-937. Exposure to hydroxyurea, thymidine, etoposide, bisbensimide, and demecolcine lead to accumulation of cells primarily in G1/S, S, S/G2/M, G2/M, and M stages of the cell cycle, respectively.

Release of anti-inflammatory mediators after mechanical trauma correlates with severity of injury and clinical outcome.

Excessive synthesis of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta] after trauma has been correlated with poor outcome. Recently, naturally occurring inhibitors of TNF-alpha and IL-1 beta have been characterized such as soluble TNF receptors (sTNFRs) and IL-1 receptor antagonist (IL-1ra). The present study was undertaken to determine whether injury results in a rise of circulating sTNFRs and IL-1ra.

[Determination of cytokines and cytokine receptors in premature labor].

One of the leading causes of preterm labour is a subclinical intrauterine infection. The diagnosis of this inapparent infection is an unsolved problem, because clinical parameters show the infection mostly too late and cannot be used for early detection of women at high risk for preterm labour. A prospective clinical study measuring cytokines and cytokine receptor concentration in amniotic fluid from patients with preterm labour and preterm rupture of membranes (PROM) was undertaken to answer the question whether the amount of cytokines is positively correlated to the risk of preterm delivery.