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Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2).

Adler H, Beland JL, Del-Pan NC, Kobzik L, Brewer JP, Martin TR, Rimm IJ - J. Exp. Med. (1997)

Bottom Line: Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival.L-NMMA treatment significantly improved survival and pulmonary compliance of HSV-1-infected mice.Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects.

View Article: PubMed Central - PubMed

Affiliation: Dana-Farber Cancer Institute, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
Intranasal Herpes simplex virus type 1 (HSV-1) infection of mice caused pneumonia. Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival. Immunohistochemical staining demonstrated iNOS induction and the nitrotyrosine antigen in the lungs of infected, but not uninfected mice, suggesting that nitric oxide contributes to the development of pneumonia. To elucidate the role of nitric oxide in the pathogenesis of HSV-1 pneumonia, infected mice were treated either with the inhibitor of nitric oxide synthase activity, N(G)-monomethyl-L-arginine (L-NMMA), or, as a control, with PBS or D-NMMA. L-NMMA treatment decreased the histological evidence of pneumonia and reduced the bronchoalveolar lavage lymphocyte number to one-quarter of the total measured in control-treated mice. L-NMMA treatment significantly improved survival and pulmonary compliance of HSV-1-infected mice. Strikingly, the L-NMMA-mediated suppression of pneumonia occurred despite the presence of a 17-fold higher pulmonary viral titer. Taken together, these data demonstrated a previously unrecognized role of nitric oxide in HSV-1-induced pneumonia. Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects.

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Treatment with l-NMMA led to a significant higher pulmonary  viral titer. Animals were treated from day 0 until analysis with l-NMMA  (triangles) or PBS (circles). Each data point represents the pulmonary viral  titer (Log PFU/Lung) obtained from an individual animal. The means for  the groups are shown by the solid lines. The viral titer in the l-NMMA– treated group at day 3 post infection was significantly higher than in PBStreated animals. The difference in viral titer per lung between the l-NMMA  and PBS group was significant (P = 0.0199 using ANOVA).
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Figure 5: Treatment with l-NMMA led to a significant higher pulmonary viral titer. Animals were treated from day 0 until analysis with l-NMMA (triangles) or PBS (circles). Each data point represents the pulmonary viral titer (Log PFU/Lung) obtained from an individual animal. The means for the groups are shown by the solid lines. The viral titer in the l-NMMA– treated group at day 3 post infection was significantly higher than in PBStreated animals. The difference in viral titer per lung between the l-NMMA and PBS group was significant (P = 0.0199 using ANOVA).

Mentions: To assess the role of NO in the antiviral defense, pulmonary viral titers were determined at days 2, 3, 4, and 7 after infection. Similar viral titers were observed at day 2 after infection between mice treated either with l-NMMA or PBS (Fig. 5). However, a 17-fold higher pulmonary viral titer was observed at day 3 in the l-NMMA–treated mice, when compared to mice treated with PBS. At day 4 after infection, a 2.5-fold higher viral titer was measured in the l-NMMA–treated mice. Virus was cleared at day 7 after infection in all groups of mice. The difference in pulmonary viral titer between the l-NMMA and PBS group was significant.


Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2).

Adler H, Beland JL, Del-Pan NC, Kobzik L, Brewer JP, Martin TR, Rimm IJ - J. Exp. Med. (1997)

Treatment with l-NMMA led to a significant higher pulmonary  viral titer. Animals were treated from day 0 until analysis with l-NMMA  (triangles) or PBS (circles). Each data point represents the pulmonary viral  titer (Log PFU/Lung) obtained from an individual animal. The means for  the groups are shown by the solid lines. The viral titer in the l-NMMA– treated group at day 3 post infection was significantly higher than in PBStreated animals. The difference in viral titer per lung between the l-NMMA  and PBS group was significant (P = 0.0199 using ANOVA).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196291&req=5

Figure 5: Treatment with l-NMMA led to a significant higher pulmonary viral titer. Animals were treated from day 0 until analysis with l-NMMA (triangles) or PBS (circles). Each data point represents the pulmonary viral titer (Log PFU/Lung) obtained from an individual animal. The means for the groups are shown by the solid lines. The viral titer in the l-NMMA– treated group at day 3 post infection was significantly higher than in PBStreated animals. The difference in viral titer per lung between the l-NMMA and PBS group was significant (P = 0.0199 using ANOVA).
Mentions: To assess the role of NO in the antiviral defense, pulmonary viral titers were determined at days 2, 3, 4, and 7 after infection. Similar viral titers were observed at day 2 after infection between mice treated either with l-NMMA or PBS (Fig. 5). However, a 17-fold higher pulmonary viral titer was observed at day 3 in the l-NMMA–treated mice, when compared to mice treated with PBS. At day 4 after infection, a 2.5-fold higher viral titer was measured in the l-NMMA–treated mice. Virus was cleared at day 7 after infection in all groups of mice. The difference in pulmonary viral titer between the l-NMMA and PBS group was significant.

Bottom Line: Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival.L-NMMA treatment significantly improved survival and pulmonary compliance of HSV-1-infected mice.Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects.

View Article: PubMed Central - PubMed

Affiliation: Dana-Farber Cancer Institute, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

ABSTRACT
Intranasal Herpes simplex virus type 1 (HSV-1) infection of mice caused pneumonia. Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival. Immunohistochemical staining demonstrated iNOS induction and the nitrotyrosine antigen in the lungs of infected, but not uninfected mice, suggesting that nitric oxide contributes to the development of pneumonia. To elucidate the role of nitric oxide in the pathogenesis of HSV-1 pneumonia, infected mice were treated either with the inhibitor of nitric oxide synthase activity, N(G)-monomethyl-L-arginine (L-NMMA), or, as a control, with PBS or D-NMMA. L-NMMA treatment decreased the histological evidence of pneumonia and reduced the bronchoalveolar lavage lymphocyte number to one-quarter of the total measured in control-treated mice. L-NMMA treatment significantly improved survival and pulmonary compliance of HSV-1-infected mice. Strikingly, the L-NMMA-mediated suppression of pneumonia occurred despite the presence of a 17-fold higher pulmonary viral titer. Taken together, these data demonstrated a previously unrecognized role of nitric oxide in HSV-1-induced pneumonia. Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects.

Show MeSH
Related in: MedlinePlus