The Experts below are selected from a list of 138 Experts worldwide ranked by ideXlab platform
Frederick G Hayden - One of the best experts on this subject based on the ideXlab platform.
-
Oral oseltamivir in human Experimental Influenza B infection
Antiviral therapy, 2000Co-Authors: Frederick G Hayden, Lance C. Jennings, Richard A. Robson, Gilbert Schiff, Helen C. Jackson, Brinderjeet Rana, Graham Mcclelland, David Ipe, Noel Roberts, Penelope WardAbstract:Oseltamivir is the prodrug of Ro64-0802 (GS4071), a potent and selective inhibitor of Influenza A and B virus neuraminidases. Three randomized, double-blind, placebo-controlled, parallel-group studies evaluated oral oseltamivir for early treatment (75 or 150 mg twice daily for 5 days) or prevention (75 mg once or twice daily for 7 days) of Experimental Influenza B virus infection in healthy susceptible adults. Treatment study A (n=60) demonstrated similar trends to treatment study B (n=117), in which 75 mg doses of oseltamivir introduced 24 h after inoculation reduced median area under curve (AUC) virus titre (oseltamivir, 22.7; placebo, 131.1 log 10 TCID 50 × h/ml; P=0.002) and duration of viral shedding (oseltamivir, 23.9 h; placebo, 95.8 h; P=0.0005). In prevention study C (n=58), oseltamivir did not reduce infection rates (85 versus 84%) but significantly reduced median AUC virus titre (10.0 versus 66.9 log 10 TCID 50 × h/ml; P=0.03) and duration of viral shedding (36 versus 84 h; P=0.03) compared with placebo. Oseltamivir was well tolerated. No emergence of drug-resistant variants was detected by testing last-day isolates (n=112) in neuraminidase inhibition assays. These results indicate that oseltamivir has significant antiviral activity in Experimental human Influenza B virus infection when used for prophylaxis or early treatment.
-
nasal cytokine and chemokine responses in Experimental Influenza a virus infection results of a placebo controlled trial of intravenous zanamivir treatment
The Journal of Infectious Diseases, 1999Co-Authors: Scott R Fritz, Frederick G Hayden, Amy W. Peng, David P. Calfee, Lindsey Cass, Gregory W Alvord, Warren Strober, Stephen E StrausAbstract:The local immune response to Influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers Experimentally infected with Influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 23/day for 5 days), a highly selective inhibitor of Influenza A and B virus neuraminidases, on the clinical symptoms of Influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-a, interferon-g, IL-10, monocyte chemotactic protein‐1, and macrophage inflammatory protein‐1a and ‐1b increased in response to Influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of Influenza. Influenza is an acute respiratory infection with high morbidity and significant mortality, primarily because of its complications in very young or old persons. The symptoms of Influenza include the sudden onset of malaise and fever, followed by upper and lower respiratory symptoms, myalgia, and headache. In adults, the fever and other systemic features usually last 3‐5 days, whereas respiratory symptoms, particularly a cough, may persist 1‐2 weeks. In addition to inducing constitutional symptoms, Influenza infection causes desquamation of the respiratory epithelium and provokes an acute inflammatory response, in which mononuclear cells and then neutrophils migrate into the mucosa.
-
nasal cytokine and chemokine responses in Experimental Influenza a virus infection results of a placebo controlled trial of intravenous zanamivir treatment
The Journal of Infectious Diseases, 1999Co-Authors: Scott R Fritz, Frederick G Hayden, Amy W. Peng, David P. Calfee, Lindsey Cass, Gregory W Alvord, Warren Strober, Stephen E StrausAbstract:The local immune response to Influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers Experimentally infected with Influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 2x/day for 5 days), a highly selective inhibitor of Influenza A and B virus neuraminidases, on the clinical symptoms of Influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-alpha, interferon-gamma, IL-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha and -1beta increased in response to Influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of Influenza.
-
Safety and efficacy of once daily intranasal zanamivir in preventing Experimental human Influenza A infection.
Antiviral therapy, 1999Co-Authors: David P. Calfee, Elizabeth K Hussey, Amy W. Peng, Monica C. Lobo, Frederick G HaydenAbstract:Zanamivir, a potent inhibitor of Influenza A and B virus neuraminidases, is protective against Experimental human Influenza when given intranasally twice daily. We conducted two studies to assess the pharmacokinetics and protective efficacy of a reduced frequency dosing regimen of topical zanamivir. In the first study, 36 uninfected volunteers received a single dose of zanamivir by intranasal spray (6.4 mg), intranasal drops (16 mg) or dry powder oral inhalation (10 mg). At 4 h, median nasal wash concentrations were 50-fold higher after intranasal dosing than after inhalation. Substantial levels (spray group, median 4,596 ng/ml; drop group, 1,239 ng/ml) were detected in nasal wash 48 h after intranasal dosing. In the double-blinded efficacy study, 47 sero-susceptible volunteers were randomized to receive either placebo or zanamivir intranasal spray (6.4 mg). Among the 43 subjects evaluated, decreases in viral shedding occurred in the group receiving one dose of zanamivir 4 h prior to inoculation, whereas no significant benefit was observed in those receiving a single dose 48 h prior to challenge. In the group given three daily doses, reductions were seen in viral shedding and infection. In the two regimens providing zanamivir 4 h prior to inoculation, significant reductions in nasal mucus weight were observed. Decreases in total symptom scores and the incidence of upper respiratory illness also occurred, but they did not reach statistical significance. The efficacy of a single dose of zanamivir given 4 h prior to inoculation supports the hypothesis that Influenza virus neuraminidase is essential for initial virus spread through respiratory secretions. These findings indicate that once daily dosing of zanamivir is protective against Experimental Influenza A infection.
-
Increased Interleukin-6 Levels in Nasal Lavage Samples following Experimental Influenza A Virus Infection
Clinical and Vaccine Immunology, 1998Co-Authors: Deborah A. Gentile, Frederick G Hayden, Philip Fireman, Theresa L. Whiteside, William J Doyle, David P. SkonerAbstract:Interleukin-6 (IL-6) is a pleotropic cytokine implicated in the pathogenesis of local inflammation during viral upper respiratory infections. This study determined if Experimental Influenza A virus infection causes local IL-6 production. Seventeen healthy, adult subjects were intranasally inoculated, by course drops, with a safety-tested strain of Influenza A/Kawasaki/86 (H1N1) virus. Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed once before and then daily for 8 days after the virus inoculation. Lavage samples were submitted for virus culture and were examined for IL-6 and IL-4 by enzyme-linked immunosorbent assay. The IL-6, but not IL-4, levels were significantly increased in the nasal lavage samples of the 12 subjects who shed virus but not in those of the 5 subjects who did not shed virus. Moreover, the elevations in IL-6 levels were related temporally to the development of nasal symptoms and secretions but not to systemic symptoms. These results suggest a role for locally produced IL-6 in the pathogenesis and expressed symptomatology of Influenza A virus infection.
John F. Sheridan - One of the best experts on this subject based on the ideXlab platform.
-
restraint stress alters lung gene expression in an Experimental Influenza a viral infection
Journal of Neuroimmunology, 2005Co-Authors: Andrea Engler, Sashwati Roy, Chandan K Sen, David A Padgett, John F. SheridanAbstract:In the present study the global effect of restraint stress on gene expression in the murine lung during an Experimental Influenza A/PR8 viral infection was examined. Gene expression profiling using high density oligonucleotide microarrays revealed that the expression of 95 genes was altered on day 3 post infection (p.i.), while 48 genes were altered on day 7 p.i. Restraint stress reduced and delayed the expression of specific cytokines, cell adhesion molecules and cell surface receptors indicating alterations in cell migration to the site of infection. Furthermore, mapping of the candidate genes to known pathways revealed that genes associated with host defense and immune responses, including chemotaxis and chemokine function, antigen presentation and processing, MHC class II receptor function and inflammation were the major pathways affected by restraint stress.
-
stress exacerbates age related decrements in the immune response to an Experimental Influenza viral infection
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 1998Co-Authors: David A Padgett, Robert C Maccallum, John F. SheridanAbstract:To test the hypothesis that stress exacerbates immune decrements associated with aging, the impact of restraint stress on immunosenescence was assessed using an Experimental model of Influenza A/Puerto Rico/8/34 viral infection. Beginning one day prior to infection, male C57BL/6 mice, 3 and 22 months of age, were subjected nightly to 12 hours of restraint stress. In both age groups, restraint induced a comparable increase in serum corticosterone levels. However, in contrast to the 3-month-old controls, serum corticosterone levels in 22-month-old mice returned to baseline slower after removal of the stressor. The characteristic Influenza-driven increase in cellularity of the lung and draining lymph node was decreased by age and further suppressed by stress. Natural killer cell activity and virus-specific T helper cell function were also blunted by age and almost completely abrogated by stress. Furthermore, due to the weak immune response to viral infection, aged animals subjected to stress had a lower survival rate than age-matched controls.
-
Neuroendocrine regulation of cytokine production during Experimental Influenza viral infection: effects of restraint stress-induced elevation in endogenous corticosterone.
Journal of immunology (Baltimore Md. : 1950), 1996Co-Authors: Cathleen M. Dobbs, N Feng, F.m. Beck, John F. SheridanAbstract:A murine model of Influenza viral infection was used to examine the neuroendocrine regulation of cytokine production. Restraint stress (RST) was used to activate the hypothalamic-pituitary-adrenal axis and elevate corticosterone (CORT) levels in Influenza A/Puerto Rico/8/34 (PR8) virus-infected C57BL/6 mice. The type II glucocorticoid receptor antagonist RU486 was used to specifically examine the modulation of PR8 virus-specific cytokine responses by CORT. RST suppressed the PR8 virus- specific production of Th1-type (IL-2 and IFN-gamma) and Th2-type IL-10) cytokines by cells from the regional lymph nodes and spleens. In addition, IL-6 production by splenocytes was inhibited by RST; however, IL-6 production by cells from the regional lymph nodes was enhanced. Treatment of mice with RU486 prevented the effects of RST, suggesting that the RST-induced alterations in cytokine responses were mediated by CORT. Furthermore, CORT was shown to inhibit the PR8 virus-specific production of both Thl-type and Th2-type cytokines in vitro at doses corresponding to the physiologic range of free plasma CORT following hypothalamic-pituitary-adrenal axis activation.
-
stress induced glucocorticoid response modulates mononuclear cell trafficking during an Experimental Influenza viral infection
Journal of Neuroimmunology, 1995Co-Authors: Gerlinda E Hermann, F.m. Beck, John F. SheridanAbstract:Abstract The migration, distribution, and localization of lymphoid cells throughout the body is critical to the efficiency and development of the immune response. This study examined the role of endogenous glucocorticoids in mononuclear cell (MNC) trafficking during the development of an immune response to infection by Influenza A/PR8 virus. Accumulation of MNC in the draining lymph nodes and at the site of virus replication (lungs) was studied in infected mice, and infected mice subjected to a Stressor (physical restraint). The glucocorticoid antagonist, RU486, was used to block the activity of endogenous corticosterone during development of the immune response. PR8-infected mice demonstrated an elevation in circulating corticosterone regardless of whether they were treated with RU486 or a placebo. Thus, some ‘afferent’ signal associated with the infection, and/or the immune response to infection, activated the hypothalamic-pituitary-adrenal axis (HPA) and was not subject to negative feedback regulation. The initial accumulation of MNC in the draining lymph nodes and lungs during infection, however, was independent of the glucocorticoid response. Our previous studies demonstrated that virally infected animals subjected to physical restraint had highly elevated plasma corticosterone levels, suppressed lymphadenopathy, and reduced accumulation of MNC in the lungs. In the present study, RU486 treatment restored cellularity to the draining lymph nodes and enhanced accumulation of MNC in lungs of stressed, A/PR8 virus-infected mice.
-
stress induced changes attributable to the sympathetic nervous system during Experimental Influenza viral infection in dba 2 inbred mouse strain
Journal of Neuroimmunology, 1994Co-Authors: Gerlinda E Hermann, Amy C Tovar, Michael F Beck, Carl M Allen, William B Malarkey, John F. SheridanAbstract:Abstract The murine model of Influenza viral infection was used to evaluate the effects of restraint stress on pathogenesis and survival in the DBA/2 inbred strain of mice. Restraint stress has been associated with an enhanced probability of survival during Influenza infection in this strain of mouse. Previous studies suggested that the protective mechanism(s) of stress on mortality might be attributable to elevated levels of circulating glucocorticoids. Subsequent work demonstrated that corticosterone levels alone could not account for the enhanced survival seen in the DBA/2 mice. The present studies examined the role of catecholamines in behavioral stress during Influenza infection. It appears that glucocorticoids may play a primary role in trafficking and restriction of inflammation, while catecholamines may play role in limiting activation of virus-specific effector cells. The studies presented here suggested that the interplay between these two physiological response mechanisms needs to be coordinated to optimize development of the immune response to an infection.
Stephen E Straus - One of the best experts on this subject based on the ideXlab platform.
-
nasal cytokine and chemokine responses in Experimental Influenza a virus infection results of a placebo controlled trial of intravenous zanamivir treatment
The Journal of Infectious Diseases, 1999Co-Authors: Scott R Fritz, Frederick G Hayden, Amy W. Peng, David P. Calfee, Lindsey Cass, Gregory W Alvord, Warren Strober, Stephen E StrausAbstract:The local immune response to Influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers Experimentally infected with Influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 23/day for 5 days), a highly selective inhibitor of Influenza A and B virus neuraminidases, on the clinical symptoms of Influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-a, interferon-g, IL-10, monocyte chemotactic protein‐1, and macrophage inflammatory protein‐1a and ‐1b increased in response to Influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of Influenza. Influenza is an acute respiratory infection with high morbidity and significant mortality, primarily because of its complications in very young or old persons. The symptoms of Influenza include the sudden onset of malaise and fever, followed by upper and lower respiratory symptoms, myalgia, and headache. In adults, the fever and other systemic features usually last 3‐5 days, whereas respiratory symptoms, particularly a cough, may persist 1‐2 weeks. In addition to inducing constitutional symptoms, Influenza infection causes desquamation of the respiratory epithelium and provokes an acute inflammatory response, in which mononuclear cells and then neutrophils migrate into the mucosa.
-
nasal cytokine and chemokine responses in Experimental Influenza a virus infection results of a placebo controlled trial of intravenous zanamivir treatment
The Journal of Infectious Diseases, 1999Co-Authors: Scott R Fritz, Frederick G Hayden, Amy W. Peng, David P. Calfee, Lindsey Cass, Gregory W Alvord, Warren Strober, Stephen E StrausAbstract:The local immune response to Influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers Experimentally infected with Influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 2x/day for 5 days), a highly selective inhibitor of Influenza A and B virus neuraminidases, on the clinical symptoms of Influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-alpha, interferon-gamma, IL-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha and -1beta increased in response to Influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of Influenza.
David P. Calfee - One of the best experts on this subject based on the ideXlab platform.
-
nasal cytokine and chemokine responses in Experimental Influenza a virus infection results of a placebo controlled trial of intravenous zanamivir treatment
The Journal of Infectious Diseases, 1999Co-Authors: Scott R Fritz, Frederick G Hayden, Amy W. Peng, David P. Calfee, Lindsey Cass, Gregory W Alvord, Warren Strober, Stephen E StrausAbstract:The local immune response to Influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers Experimentally infected with Influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 2x/day for 5 days), a highly selective inhibitor of Influenza A and B virus neuraminidases, on the clinical symptoms of Influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-alpha, interferon-gamma, IL-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1alpha and -1beta increased in response to Influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of Influenza.
-
nasal cytokine and chemokine responses in Experimental Influenza a virus infection results of a placebo controlled trial of intravenous zanamivir treatment
The Journal of Infectious Diseases, 1999Co-Authors: Scott R Fritz, Frederick G Hayden, Amy W. Peng, David P. Calfee, Lindsey Cass, Gregory W Alvord, Warren Strober, Stephen E StrausAbstract:The local immune response to Influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid samples from 15 volunteers Experimentally infected with Influenza A/Texas/36/91 (H1N1). The study was part of a randomized double-blind placebo-controlled trial to determine the prophylactic effect of intravenous zanamivir (600 mg 23/day for 5 days), a highly selective inhibitor of Influenza A and B virus neuraminidases, on the clinical symptoms of Influenza infection. Nasal lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-a, interferon-g, IL-10, monocyte chemotactic protein‐1, and macrophage inflammatory protein‐1a and ‐1b increased in response to Influenza virus infection and correlated statistically with the magnitude and time course of the symptoms. Treatment with zanamivir prevented the infection and abrogated the local cytokine and chemokine responses. These results reveal a complex interplay of cytokines and chemokines in the development of symptoms and resolution of Influenza. Influenza is an acute respiratory infection with high morbidity and significant mortality, primarily because of its complications in very young or old persons. The symptoms of Influenza include the sudden onset of malaise and fever, followed by upper and lower respiratory symptoms, myalgia, and headache. In adults, the fever and other systemic features usually last 3‐5 days, whereas respiratory symptoms, particularly a cough, may persist 1‐2 weeks. In addition to inducing constitutional symptoms, Influenza infection causes desquamation of the respiratory epithelium and provokes an acute inflammatory response, in which mononuclear cells and then neutrophils migrate into the mucosa.
-
Safety and efficacy of once daily intranasal zanamivir in preventing Experimental human Influenza A infection.
Antiviral therapy, 1999Co-Authors: David P. Calfee, Elizabeth K Hussey, Amy W. Peng, Monica C. Lobo, Frederick G HaydenAbstract:Zanamivir, a potent inhibitor of Influenza A and B virus neuraminidases, is protective against Experimental human Influenza when given intranasally twice daily. We conducted two studies to assess the pharmacokinetics and protective efficacy of a reduced frequency dosing regimen of topical zanamivir. In the first study, 36 uninfected volunteers received a single dose of zanamivir by intranasal spray (6.4 mg), intranasal drops (16 mg) or dry powder oral inhalation (10 mg). At 4 h, median nasal wash concentrations were 50-fold higher after intranasal dosing than after inhalation. Substantial levels (spray group, median 4,596 ng/ml; drop group, 1,239 ng/ml) were detected in nasal wash 48 h after intranasal dosing. In the double-blinded efficacy study, 47 sero-susceptible volunteers were randomized to receive either placebo or zanamivir intranasal spray (6.4 mg). Among the 43 subjects evaluated, decreases in viral shedding occurred in the group receiving one dose of zanamivir 4 h prior to inoculation, whereas no significant benefit was observed in those receiving a single dose 48 h prior to challenge. In the group given three daily doses, reductions were seen in viral shedding and infection. In the two regimens providing zanamivir 4 h prior to inoculation, significant reductions in nasal mucus weight were observed. Decreases in total symptom scores and the incidence of upper respiratory illness also occurred, but they did not reach statistical significance. The efficacy of a single dose of zanamivir given 4 h prior to inoculation supports the hypothesis that Influenza virus neuraminidase is essential for initial virus spread through respiratory secretions. These findings indicate that once daily dosing of zanamivir is protective against Experimental Influenza A infection.
Gerlinda E Hermann - One of the best experts on this subject based on the ideXlab platform.
-
stress induced glucocorticoid response modulates mononuclear cell trafficking during an Experimental Influenza viral infection
Journal of Neuroimmunology, 1995Co-Authors: Gerlinda E Hermann, F.m. Beck, John F. SheridanAbstract:Abstract The migration, distribution, and localization of lymphoid cells throughout the body is critical to the efficiency and development of the immune response. This study examined the role of endogenous glucocorticoids in mononuclear cell (MNC) trafficking during the development of an immune response to infection by Influenza A/PR8 virus. Accumulation of MNC in the draining lymph nodes and at the site of virus replication (lungs) was studied in infected mice, and infected mice subjected to a Stressor (physical restraint). The glucocorticoid antagonist, RU486, was used to block the activity of endogenous corticosterone during development of the immune response. PR8-infected mice demonstrated an elevation in circulating corticosterone regardless of whether they were treated with RU486 or a placebo. Thus, some ‘afferent’ signal associated with the infection, and/or the immune response to infection, activated the hypothalamic-pituitary-adrenal axis (HPA) and was not subject to negative feedback regulation. The initial accumulation of MNC in the draining lymph nodes and lungs during infection, however, was independent of the glucocorticoid response. Our previous studies demonstrated that virally infected animals subjected to physical restraint had highly elevated plasma corticosterone levels, suppressed lymphadenopathy, and reduced accumulation of MNC in the lungs. In the present study, RU486 treatment restored cellularity to the draining lymph nodes and enhanced accumulation of MNC in lungs of stressed, A/PR8 virus-infected mice.
-
stress induced changes attributable to the sympathetic nervous system during Experimental Influenza viral infection in dba 2 inbred mouse strain
Journal of Neuroimmunology, 1994Co-Authors: Gerlinda E Hermann, Amy C Tovar, Michael F Beck, Carl M Allen, William B Malarkey, John F. SheridanAbstract:Abstract The murine model of Influenza viral infection was used to evaluate the effects of restraint stress on pathogenesis and survival in the DBA/2 inbred strain of mice. Restraint stress has been associated with an enhanced probability of survival during Influenza infection in this strain of mouse. Previous studies suggested that the protective mechanism(s) of stress on mortality might be attributable to elevated levels of circulating glucocorticoids. Subsequent work demonstrated that corticosterone levels alone could not account for the enhanced survival seen in the DBA/2 mice. The present studies examined the role of catecholamines in behavioral stress during Influenza infection. It appears that glucocorticoids may play a primary role in trafficking and restriction of inflammation, while catecholamines may play role in limiting activation of virus-specific effector cells. The studies presented here suggested that the interplay between these two physiological response mechanisms needs to be coordinated to optimize development of the immune response to an infection.
-
kinetics of glucocorticoid response to restraint stress and or Experimental Influenza viral infection in two inbred strains of mice
Journal of Neuroimmunology, 1994Co-Authors: Gerlinda E Hermann, Amy C Tovar, Michael F Beck, John F. SheridanAbstract:The murine model of Influenza viral infection was used to evaluate the effects of restraint stress on pathogenesis and survival in inbred strains of mice. We recently reported that restraint stress was associated with an enhanced probability of survival in one strain of inbred mouse, DBA/2, and not in another, C57BL/6. Those studies suggested that the protective mechanism(s) of stress on mortality in the DBA/2 mice might be attributable to elevated levels of circulating glucocorticoids. Therefore, daily levels of plasma glucocorticoids were measured during Influenza viral infection in both these strains. The present studies demonstrated that Influenza infection itself is perceived as a stressor in both C57BL/6 and DBA/2 mice as evidenced by elevated plasma glucocorticoid levels within 48 h of infection. However, augmentation of glucocorticoid levels was not seen in the DBA/2 mice that were also subjected to restraint stress during the course of infection. Thus, corticosterone levels alone did not account for the enhanced survival seen in this group of animals.
-
restraint stress differentially affects the pathogenesis of an Experimental Influenza viral infection in three inbred strains of mice
Journal of Neuroimmunology, 1993Co-Authors: Gerlinda E Hermann, Amy C Tovar, Michael F Beck, Carl M Allen, John F. SheridanAbstract:Abstract Genetic variation in the response to stress may play a critical role in susceptibility to inflammatory diseases and development of the immune response. Experimental Influenza viral infection was used to study the effects of restraint stress (RST) on pathogenesis and development of the immune response. Three inbred strains of mice (C57BL/6, DBA/2, and C3H/HeN) were infected with Influenza A/PR8 and subjected to repetitive cycles of RST during development of the immune response. RST diminished cellular immune and inflammatory response in all three strains; yet only the DBA/2 strain demonstrated RST-associated reduction in Influenza viral-induced mortality.
