Tumor necrosis factor as a mediator of inflammation in influenza A viral pneumonia

Peper, Randall L.; Campen, Hana Van

doi:10.1006/mpat.1995.0056

Cited by 127 publications

(107 citation statements)

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“…Although therapeutic treatment of uninfected B6 mice with PTX3 does not enhance serum cytokine levels (data not shown), others have reported PTX3 to facilitate production of cytokines in an inflammatory or infectious environment (43,44). Future studies will determine the effect of therapeutic PTX3 treatment on the production of proinflammatory cytokines in the airways during infection with PTX3 S /PTX3 R virus strains; cytokines such as TNF-␣ have been reported to modulate influenza virus-induced inflammation and to mediate direct antiviral activity (45,46). The PTX3 R PR8 virus did, however, grow to similar titers in mouse lung in PTX3 ϩ/ϩ and PTX3 Ϫ/Ϫ mice (Fig.…”

Section: Discussionmentioning

confidence: 94%

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Reading

Bozza

Gilbertson

et al. 2008

The Journal of Immunology

180

212

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Proteins of the innate immune system can act as natural inhibitors of influenza virus, limiting growth and spread of the virus in the early stages of infection before the induction of adaptive immune responses. In this study, we identify the long pentraxin PTX3 as a potent innate inhibitor of influenza viruses both in vitro and in vivo. Human and murine PTX3 bound to influenza virus and mediated a range of antiviral activities, including inhibition of hemagglutination, neutralization of virus infectivity and inhibition of viral neuraminidase. Antiviral activity was associated with binding of the viral hemagglutinin glycoprotein to sialylated ligands present on PTX3. Using a mouse model we found PTX3 to be rapidly induced following influenza infection and that PTX3−/− mice were more susceptible than wild-type mice to infection by PTX3-sensitive virus strains. Therapeutic treatment of mice with human PTX3 promoted survival and reduced viral load in the lungs following infection with PTX3-sensitive, but not PTX3-resistant, influenza viruses. Together, these studies describe a novel antiviral role for PTX3 in early host defense against influenza infections both in vitro and in vivo and describe the therapeutic potential of PTX3 in ameliorating disease during influenza infection.

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Section: Discussionmentioning

confidence: 94%

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Reading

Bozza

Gilbertson

et al. 2008

The Journal of Immunology

180

212

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“…Until now, the association between cytokines and influenza pneumonia has been studied exclusively in mice, which are not natural influenza virus hosts. In this murine model, there is an early increase of both TNF-α and IL-1 [59,99,131] in bronchoalveolar lavage fluids (BAL), and cytokines correlate with the characteristic signs of disease (lethargy, anorexia, followed by mortality) and with mononuclear cell infiltration in the lungs and gross lesion development. In a study by Hennet et al [59], production of TNF-α/IL-1 was followed by that of other cytokines and inflammatory products: IL-6, granulocyte macrophage-colony stimulating factor, IFN-γ and leukotriene B4.…”

Section: Cytokines In Viral Respiratory Diseases Of Humansmentioning

confidence: 99%

“…The role of individual cytokines during influenza in mice was assessed only recently by specific anti-cytokine strategies. Intraperitoneal administration of TNF antibodies at the time of influenza inoculation reduces lung lesion severity and prolongs survival by 24 h [99]. In IL-1β gene knock-out mice, influenza inoculation has a smaller effect on body temperature than in wild type mice, but anorexia and weight loss are similar [68].…”

Section: Cytokines In Viral Respiratory Diseases Of Humansmentioning

confidence: 99%

Proinflammatory cytokines and viral respiratory disease in pigs

2000

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-Swine influenza virus (SIV), porcine respiratory coronavirus (PRCV) and porcine reproductive and respiratory syndrome virus (PRRSV) are enzootic viruses causing pulmonary infections in pigs. The first part of this review concentrates on known clinical and pathogenetic features of these infections. SIV is a primary respiratory pathogen; PRCV and PRRSV, on the contrary, tend to cause subclinical infections if uncomplicated but they appear to be important contributors to multifactorial respiratory diseases. The exact mechanisms whereby these viruses cause symptoms and pathology, however, remain unresolved. Classical studies of pathogenesis have revealed different lung cell tropisms and replication kinetics for each of these viruses and they suggest the involvement of different lung inflammatory responses or mediators. The proinflammatory cytokines interferon-α (IFN-α), tumour necrosis factor-α (TNF-α) and interleukin-1 (IL-1) have been shown to play key roles in several respiratory disease conditions. The biological effects of these cytokines and their involvement in human viral respiratory disease are discussed in the second part of this review. The third part summarises studies that were recently undertaken in the authors' laboratory to investigate the relationship between respiratory disease in pigs and bioactive lung lavage levels of IFN-α, TNF-α and IL-1 during single and combined infections with the above viruses. In single SIV infections, typical signs of swine "flu" were tightly correlated with an excessive and coordinate production of the 3 cytokines examined. PRCV or PRRSV infections, in contrast, were subclinical and did not induce production of all 3 cytokines. Combined infections with these 2 subclinical respiratory viruses failed to potentiate disease or cytokine production. After combined inoculation with PRCV followed by bacterial lipopolysaccharide, both clinical respiratory disease and TNF-α/IL-1 production were markedly more severe than those associated with the respective single inoculations. Taken together, these data are the first to demonstrate that proinflammatory cytokines can be important mediators of viral respiratory diseases in pigs. respiratory coronavirus, PRCV), et le virus du syndrome dysgénésique et respiratoire porcin (porcine reproductive and respiratory syndrome virus, PRRSV) sont des virus enzootiques provoquant des infections pulmonaires chez le porc. Les caractéristiques cliniques et pathogénétiques de ces infections sont données dans la première partie de cette revue. Le SIV est un agent pathogène respiratoire primaire ; les PRCV et PRRSV, en revanche, ne causent que des infections subcliniques en l'absence de complications, mais ils contribuent de manière importante aux maladies respiratoires multifactorielles. Cependant, les mécanismes précis par lesquels ces virus provoquent des symptômes et une pathologie demeurent inconnus. Les études classiques de pathogenèse ont révélé un tropisme pour les cellules pulmonaires et des cinétiques de réplication différents pour...

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“…Mice deficient in NO synthase 2 (NOS2) 5 or TNF-␣ display decreased mortality when infected with mouse-adapted influenza (11)(12)(13). This increased survival appears to occur because NOS2 and TNF-␣ induce significant lung damage, but contribute little to anti-influenza immune responses (14,15).…”

mentioning

confidence: 99%

CCR2+ Monocyte-Derived Dendritic Cells and Exudate Macrophages Produce Influenza-Induced Pulmonary Immune Pathology and Mortality

Lin¹,

Suzuki²,

Nakano³

et al. 2008

The Journal of Immunology

408

487

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Infection with pathogenic influenza virus induces severe pulmonary immune pathology, but the specific cell types that cause this have not been determined. We characterized inflammatory cell types in mice that overexpress MCP-1 (CCL2) in the lungs, then examined those cells during influenza infection of wild-type (WT) mice. Lungs of both naive surfactant protein C-MCP mice and influenza-infected WT mice contain increased numbers of CCR2+ monocytes, monocyte-derived DC (moDC), and exudate macrophages (exMACs). Adoptively transferred Gr-1+ monocytes give rise to both moDC and exMACs in influenza-infected lungs. MoDC, the most common inflammatory cell type in infected lungs, induce robust naive T cell proliferation and produce NO synthase 2 (NOS2), whereas exMACs produce high levels of TNF-α and NOS2 and stimulate the proliferation of memory T cells. Relative to WT mice, influenza-infected CCR2-deficient mice display marked reductions in the accumulation of monocyte-derived inflammatory cells, cells producing NOS2, the expression of costimulatory molecules, markers of lung injury, weight loss, and mortality. We conclude that CCR2+ monocyte-derived cells are the predominant cause of immune pathology during influenza infection and that such pathology is markedly abrogated in the absence of CCR2.

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Tumor necrosis factor as a mediator of inflammation in influenza A viral pneumonia

Cited by 127 publications

References 0 publications

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

Proinflammatory cytokines and viral respiratory disease in pigs

CCR2+ Monocyte-Derived Dendritic Cells and Exudate Macrophages Produce Influenza-Induced Pulmonary Immune Pathology and Mortality

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