Exacerbation of acute and chronic murine tuberculosis by administration of a tumor necrosis factor receptor-expressing adenovirus.

Tumor necrosis factor (TNF) plays a pivotal role in inflammatory phenomena that culminate in either pathogenesis or resistance in mycobacterial disease. The regulatory role of TNF in murine tuberculosis was examined by administering a recombinant adenovirus encoding a fusion protein consisting of the human 55-kDa TNF receptor extracellular domain and the mouse IgG heavy chain domain (AdTNFR). During acute infections with Mycobacterium tuberculosis, AdTNFR pretreatment induced elevated mycobacterial burdens of 1 log10 in the tissues of H37Ra-infected mice and 2 log10 (spleen and liver) and 4 log10 (lungs) in H37Rv-infected mice.

Independent suppression of nitric oxide and TNF alpha in the lung of conscious rats by ethanol.

Tumor necrosis factor-alpha (TNF alpha) and nitric oxide (NO) mediate in part the microbicidal response of murine and rodent alveolar macrophages (AM) and recruited neutrophils (PMN) to airborne infections. Ethanol (ETOH) suppresses intrapulmonary TNF alpha and NO release and impairs pulmonary host defense mechanisms. We tested the concept that ETOH down-regulates NO by inhibiting production of TNF alpha.

In vivo administration of endotoxin and tumor necrosis factor-alpha produce different effects on constitutive and inducible nitric oxide synthase activity in rat neutrophils and aorta ex vivo.

Tumor necrosis factor-alpha (TNF-alpha) inhibits release of nitric oxide (NO) in vitro by stimulating the degradation of constitutive NO synthase (cNOS III) mRNA. However, TNF-alpha is believed to be the cytokine mediator of the hypotension and upregulation of inducible NO synthase (iNOS II) produced by gram-negative bacterial endotoxin (LPS). Some in vivo effects of TNF-alpha are opposite to those which occur in vitro.

Ethanol suppresses LPS-induced mRNA for nitric oxide synthase II in alveolar macrophages in vivo and in vitro.

Alcohol abuse increases the incidence and severity of opportunistic lung infections and pneumonias. Inducible nitric oxide (NO) synthase (iNOS II) and NO may be a pivotal system in the intracellular bactericidal activity of macrophages. We tested the hypothesis that acute administration of ethanol (ETOH) suppressed Escherichia coli endotoxin lipopolysaccharide (LPS) mediated upregulation of the iNOS II system in the lung of the rat, in vivo.

Rapid induction of messenger RNA for nitric oxide synthase II in rat neutrophils in vivo by endotoxin and its suppression by prednisolone.

Nitric oxide is believed to participate in nonspecific cellular immunity. Gram negative bacterial endotoxins increase the production of reactive nitrogen intermediates (RNI) in phagocytic cells by inducing the enzyme nitric oxide synthase II (NOS II). Anti-inflammatory glucocorticoids attenuate endotoxin-induced increases in RNI.

Prolonged and effective blockade of tumor necrosis factor activity through adenovirus-mediated gene transfer.

A chimeric protein capable of binding and neutralizing tumor necrosis factor (TNF) and lymphotoxin was expressed in mice transduced with a replication-incompetent adenoviral vector into which a TNF inhibitor gene had been engineered. Within 3 days following the injection of 10(9) infectious particles, the TNF inhibitor concentration exceeded 1 mg/ml of plasma; this level of expression was maintained for at least 4 weeks, and detectable TNF inhibitory activity was measured 6 weeks after injection of the recombinant virus. Introduction of the artificial gene produced a phenotypic effect comparable to homozygous deletion of the 55-kDa TNF receptor, in that animals were rendered highly susceptible to infection by Listeria monocytogenes, whereas control animals receiving a replication-incompetent virus coding for beta-galactosidase were capable of resisting Listeria challenge.

Alcohol administration attenuates LPS-induced expression of inducible nitric oxide synthase in Kupffer and hepatic endothelial cells.

This study investigates the effects of in vivo ethanol (primed infusion, causing 170-190 mg% plasma alcohol for 12 hours) and/or LPS (12 hours after injection of E. coli LPS 1 mg/kg bw.) on the mRNA expression of inducible nitric oxide synthase (NOS II) in hepatic cells measured by competitive PCR technique, and on hepatic release of reactive nitrogen intermediates (RNI, NO2- + NO3-).

Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages.

Thirteen previously healthy children with acute onset of severe lower respiratory tract signs and symptoms underwent bronchoscopy and bronchoalveolar lavage (BAL) for diagnostic purposes. BAL samples were assessed for viral, bacterial, mycobacterial, and fungal cultures. Cytospin preparations of BAL cells were assessed for expression of respiratory syncytial virus (RSV), HLA-DR, interleukin-1 beta, and tumor necrosis factor proteins.

Recombinant cytokines and pulmonary host defense.

The recent discovery of several cytokines and their purification using recombinant DNA technology has uncovered their role as critical factors in pulmonary host defense. The importance of tumor necrosis factor, interferon-gamma, and granulocyte-colony stimulating factor in lung infections was first elucidated in animal models and has been confirmed with neutralization studies. This article reviews these three cytokines, their recent use in human subjects, and their potential use in the future.

Tumor necrosis factor inhibits stimulated but not basal release of nitric oxide.

Tumor necrosis factor alpha (TNF alpha) increases nitric oxide (NO) synthase in vascular endothelium, but it inhibits endothelium-dependent relaxation (EDR) of vascular smooth muscle. We tested whether TNF alpha inhibits the response to, or release of, NO in bovine pulmonary artery (BPA) using the technique of perfusion-superfusion bioassay and ozone chemiluminescence. Effluent from the perfused BPA with endothelium (donor)-relaxed endothelium-rubbed bovine coronary artery (BCA) (detector).

Tumor necrosis factor alpha inhibits contractions to sympathetic nerve stimulation by a nitric oxide-dependent mechanism.

Gram-negative sepsis and administration of tumor necrosis factor alpha (TNF alpha) are associated with hypotension and peripheral neuropathies suggestive of impaired sympathetic neurotransmission. We examined the effect of TNF alpha on the responses of the bovine pulmonary artery (BPA) to transmural sympathetic nerve stimulation (SNS). BPA contracted to SNS (0.

Tumor necrosis factor-alpha inhibits endothelium-dependent relaxation.

Tumor necrosis factor-alpha (TNF-alpha) stimulates nitric oxide (NO) in vascular endothelium by induction of the enzyme NO synthase II (NOS II). We examined the effects of TNF-alpha on 1) endothelium-dependent (EDR) and endothelium-independent (EIR) relaxation and 2) contraction of bovine intralobar pulmonary arteries (BPA) and veins (BPV) in vitro. Acetylcholine (ACh), bradykinin (BK), histamine, and A23187 produced EDR of BPA contracted with a 50% effective concentration of U-46619 (15 nM), because relaxation was abolished by endothelium-rubbing and attenuated by L-NG-mono-methylarginine (L-NMMA; 300 microM).

Alveolar macrophage release of tumor necrosis factor during murine Pneumocystis carinii pneumonia.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine produced principally by mononuclear cells, is released in response to a variety of pulmonary pathogens. We hypothesized that release of TNF in the lung is a normal part of the host response to intratracheal challenge with Pneumocystis carinii. To test this hypothesis, we measured TNF in bronchoalveolar lavage fluid (BALF) in normal and CD4-depleted mice at various intervals in acute and chronically infected animals.

cDNA equalization for reverse transcription-polymerase chain reaction quantitation.

Reverse transcription coupled with the polymerase chain reaction has been increasingly utilized to study gene expression. However, most previously published quantitative techniques are limited by accurate initial RNA quantitation and do not account well for the relative efficiency of reverse transcription. We have developed a technique of labeling and quantitating the random-primed cDNA product of a reverse transcription reaction.

Ethanol relaxes pulmonary artery by release of prostaglandin and nitric oxide.

Acute-intake of ethanol is associated with vasodilation of vascular smooth muscle (VSM). Relaxation of VSM is dependent, in part, on the actions of nitric oxide (NO) and prostaglandin (PG) produced by endothelial cells (EC) lining the VSM. We examined the effects of endothelium rubbing and inhibition of EC synthesis of NO and PG on ethanol-induced relaxation of bovine pulmonary artery (BPA) and pulmonary vein (BPV) in vitro.

Intralobar pulmonary sequestration presenting as congestive heart failure in a neonate.

We recently evaluated a premature infant with intralobar pulmonary sequestration which presented with signs of CHF. The infant initially underwent ligation of a PDA but subsequently developed tachycardia, tachypnea, and a continuous murmur which radiated to the back. The diagnosis of a pulmonary sequestration was suggested by Doppler echocardiography and confirmed by aortography.