Granulocyte colony-stimulating factor and antibiotics in the prophylaxis of a murine model of polymicrobial peritonitis and sepsis.

Infections that occur after intraabdominal surgery still cause considerable morbidity and mortality despite the administration of prophylactic antibiotics. Increasing the number of neutrophils may also be a prophylactic approach, and granulocyte colony-stimulating factor (G-CSF) has been found to be beneficial in different animal models of peritonitis and sepsis. It is the combination of G-CSF and antibiotics, however, that is clinically relevant.

Epirubicin/vinorelbine as first line therapy in metastatic breast cancer.

This study was aimed at investigating the toxicity and activity of the combination epirubicin and vinorelbine in chemotherapy-naive patients with metastatic breast cancer. Fifty-one patients with measurable or evaluable metastatic breast cancer entered the study. The regimen consisted of epirubicin 90 mg/m2 as a slow i.

Tumor necrosis factor is increased in the spinal cord of an animal model of motor neuron degeneration.

Autoimmunity and oxidative/excitotoxic damage are considered as possible pathogenetic mechanisms in amyotrophic lateral sclerosis (ALS). As tumor necrosis factor (TNF) is implicated in autoimmune diseases, including experimental autoimmune encephalomyelitis, and can be neurotoxic, we studied TNF production in a proposed animal model of ALS, the mnd mouse. These mice develop symptoms (progressive weakness of the limbs) as late as at 7 months of age.

Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: action mechanisms and role of CNTF receptor alpha.

Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS lethality when coadministered with its soluble receptor (sCNTFR alpha). Both of these activities are abolished in adrenalectomized (ADX) mice. LPS-induced pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO) production were also inhibited by CNTF + sCNTFR alpha but not by CNTF alone.

Centrally mediated inhibition of local inflammation by ciliary neurotrophic factor.

Since ciliary neurotrophic factor (CNTF) inhibits the production of TNF and activates the hypothalamus-pituitary-adrenal axis (HPAA), we investigated whether CNTF can produce antiinflammatory actions and whether it may act through a central mechanism, using the murine air pouch model of inflammation. In this model, inflammation is evaluated by measuring the induction of TNF and IL-6 as well as cell recruitment in the pouch fluid 24 h after carrageenan. Intracerebroventricular injection, but not intravenous or local injection of CNTF markedly inhibited inflammation.

Removal of cytokines and activated complement components in an experimental model of continuous plasma filtration coupled with sorbent adsorption.

Background: Sepsis is associated with enhanced cytokine production. Here, we examined the in vitro removal of plasma cytokines during continuous plasmafiltration coupled with sorbent adsorption.

Methods: Proinflammatory (tumour necrosis factor-alpha, interleukins-1, -8) and anti-inflammatory (interleukin 1 receptor antagonist, soluble tumour necrosis factor receptor type I and II) cytokines in whole blood spiked with Escherichia coli endotoxin were determined during 2-h recirculation in the ultrafiltrate (condition A), plasma filtrate (condition B), before and after different sorbents (of the Amberlite-, Amberchrome- Ambersorb -type and charcoal).

Mycobacterial Cpn10 promotes recognition of the mammalian homologue by a mycobacterium-specific antiserum.

Self-tolerance, a key feature of the immune system, is still a matter of intense debate. We give here evidence for a peculiar behavior of an antiserum against Mycobacterium tuberculosis chaperonin 10 (m-Cpn10), which could have implications for the mechanism of self-recognition by antibodies against non-self. We show that this antiserum can interact in terms of both inhibition of biological activity and physical association (immunoprecipitation), with the mammalian homologue of m-Cpn10, but only if the bacterial protein is present.

Regulation of inhibitory pathways of the interleukin-1 system.

The IL-1 system includes two agonists, converting enzymes, antagonists, and two receptors (R). New elements and functions in the system will be discussed, including (a) cloning of a new isoform of the receptor antagonist; (b) further analysis of the type II IL-1-binding molecule as a decoy R. The modulation of IL-1R by chemotactic signals was recently investigated.

MK 801 and dexamethasone reduce both tumor necrosis factor levels and infarct volume after focal cerebral ischemia in the rat brain.

Focal cerebral ischemia in rats produces elevated levels of tumor necrosis factor (TNF)alpha in the ischemic brain region. To better understand the modulation of TNF during brain ischemia processes we carried out studies in a model of permanent middle cerebral artery occlusion (MCAo) in the rat. In non-treated ischemic animals, the maximum expression of TNF was observed at 12 h (246.

Within-patient variability of hormone and cytokine concentrations in heart failure.

Several studies on disease and treatment effects on neurohormones have been conducted with small numbers of patients, using one blood sample as representative of their states. The aim of this study was to assess the within-patient variability of plasma concentrations of several hormones and cytokines of recent interest, in patients with moderate heart failure and controlled stable background therapy over 3 weeks. Blood for neurohormone and cytokine assays was sampled in duplicate from 18 patients with moderate heart failure.

[Vascular access in hemodialysis. Surveillance and role of percutaneous transluminal angioplasty].

The function of vascular shunts in hemodialysis plays a vital role for the efficiency and effectiveness of replacement therapy. A study was performed in 147 patients undergoing periodical hemodialysis with distal FAV (no = 86), proximal FAV (no = 33), PTFE grafts (no = 23), Canaud-Tesio catheters (no = 7). A protocol for function evaluation was developed which also included the calculation of overall recirculation (R), that was found to be 10.

Mechanism of the inhibitory effect of melatonin on tumor necrosis factor production in vivo and in vitro.

Melatonin is an antioxidant. Since other antioxidants inhibit the production of tumor necrosis factor (TNF) induced by lipopolysaccharide, we investigated its effect on TNF production in vivo and in vitro and on lethality associated with endotoxic shock. Administration of melatonin to mice (5 mg/kg, s.

Carboplatin and vinorelbine in the treatment of advanced non-small-cell lung cancer: a multicenter phase II study.

The aim of this study was to identify a chemotherapy combination that would be active and well tolerated for palliative treatment of advanced non-small-cell lung cancer (NSCLC). From February 1992 to December 1994, a total of 77 patients affected by stage-IIIB and stage-IV NSCLC were treated with carboplatin 350 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8 of each cycle, with cycles repeated every 28 days. All patients were evaluable for response and toxicity.

Systemic interleukin 10 administration inhibits brain tumor necrosis factor production in mice.

Interleukin 10 is an antiinflammatory cytokine and inhibits the production of tumor necrosis factor. We have previously found that intracerebroventricular (i.c.

Protective effect of a single interleukin-12 (IL-12) predose against the toxicity of subsequent chronic IL-12 in mice: role of cytokines and glucocorticoids.

The mechanisms of interleukin-12 (IL-12) toxicity were studied in mice using a schedule (murine rIL-12, 400 ng/mouse, intraperitoneally [IP] once daily for 5 days) that markedly reduced body weight and food intake. On day 5, IL-12-treated mice had elevated serum and spleen IFN-gamma and tumor necrosis factor (TNF). Serum sTNFR-P75 and corticosterone (CS) were also elevated.

Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia.

Two contrasting roles, one beneficial and the injurious, have been proposed for tumor necrosis factor (TNF) in the pathogenesis of cerebral ischemia. Reported here are results obtained in a standard model of permanent focal cortical ischemia in rats, in which the volume of cerebral infarction is measured after permanent occlusion of the middle cerebral artery. Administration of neutralizing anti-rat TNF antibodies (P114) into the brain cortex significantly reduced ischemic brain damage (85% reduced infarct volume as compared with preimmune-treated controls).

[Bovine leukemia virus (BLV): prevalence in the Cuenca Lechera Mar y Sierras from 1994 to 1995].

The Cuenca Lechera Mar y Sierras (CLMS) includes about 300 dairy farms located in the counties of Tandil, Balcarce, Juarez, Ayacucho, General Pueyrredón, Gonzalez Chavez and Necochea, in the province of Buenos Aires. The purpose of this investigation was to determine the prevalence of infection caused by Bovine Leukemia Virus (BLV) in the CLMS. We investigated the presence of anti-BLV antibodies in 4,203 milk samples taken from 73 dairy farms belonging to the CLMS.

Physiological and cytokine responses in IL-1 beta-deficient mice after zymosan-induced inflammation.

Interleukin (IL)-1 beta-deficient (IL-1 beta -/-) mice exhibited decreased zymosan-induced lethality and reduced production of IL-6 compared with wild-type controls (IL-1 beta +/+). In addition, IL-1 beta -/- mice had a diminished cellular infiltrate (33%) in the peritoneal cavity after zymosan. However, anorexia and hypoglycemia were not affected by the lack of IL-1 beta.

IL-13 inhibits TNF production but potentiates that of IL-6 in vivo and ex vivo in mice.

IL-13 was reported to inhibit the synthesis of various cytokines in vitro, including that of TNF. It has divergent effects on IL-6 production, which is increased in endothelial cells and decreased in monocytes. We studied the effect of IL-13 administration on TNF and IL-6 production in vivo in mice.

Differential effects of IL-6 on systemic and central production of TNF: a study with IL-6-deficient mice.

Interleukin 6 (IL-6) is known to inhibit the synthesis of tumour necrosis factor (TNF) in vitro and in vivo. In this study we investigated the possible role of IL-6 as an endogenous inhibitor of TNF production in the brain or in the periphery using IL-6-deficient mice or administering recombinant human IL-6 (rhIL-6). When IL-6-deficient mice were injected intracerebroventricularly (i.

Hyperresponsive febrile reactions to interleukin (IL) 1alpha and IL-1beta, and altered brain cytokine mRNA and serum cytokine levels, in IL-1beta-deficient mice.

IL-1beta is an endogenous pyrogen that is induced during systemic lipopolysaccharide (LPS)- or IL-1-induced fever. We have examined the fever and cytokine responses following i.p.

Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment.

IL-6-/- mice showed impaired leukocyte accumulation in subcutaneous air pouches. Defective leukocyte accumulation was not due to a reduced migratory capacity of IL-6-/- leukocytes and was associated with a reduced in situ production of chemokines. These observations led to a reexamination of the interaction of IL-6 with endothelial cells (EC).

Carrageenan-induced acute inflammation in the mouse air pouch synovial model. Role of tumour necrosis factor.

We used the mouse air pouch model of inflammation to study the interaction between cytokines, prostaglandin E(2) (PGE(2)) and cell migration during the various phases of acute local inflammation induced by carrageenan. In serum, the levels of interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor (TNF), serum amiloid-A (SAA) and Fe(++) were never different from controls, indicating that no systemic inflammatory changes were induced. Locally the exudate volume and the number of leukocytes recruited into the pouch increased progressively until 7 days after carrageenan.