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Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection
e4
Abstracts
milkdrink once daily for 6 weeks. Both probiotic products contained a minimum of one billion Colony Forming Units per dose. After two weeks subjects received an influenza vaccination. Plasma and saliva samples were collected at baseline and after 6 weeks for analysis of vaccinespecific and total antibodies, cytokines IL-2, IL-10 and INF-γ, and innate immune parameters. Results: The vaccine-specific antibody responses were significantly increased in both probiotic groups compared to their corresponding placebo group (Fig. 1).
A
Conclusions: Both probiotic strains increased the specific and total antibody response to an influenza vaccine. BB-12® and L. casei 431® may increase the body's resistance to common infections by strengthening both mucosal and systemic immunity. Keywords: Probiotics, Immune response, Vaccination, Clinical Trial References 1. Cummings, J.H., et al., 2004. PASSCLAIM – Gut health and immunity. Eur. J. Nutr. 43 (suppl 2), II/118–II/173. 2. Stepanova, L., et al., 2002. The humoral response to live and inactivated influenza vaccines administered alone and in combination to young adults and elderly. J. Clin. Virol. 24, 193–201. 3. Kurstak, E., 1985. Progress in enzyme immunoassays: production of reagents, experimental design, and interpretation. Bull. World Health Organ. 63, 793–811. doi:10.1016/j.ejphar.2011.09.200
Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection A. Taylor, W. Cao, S. Zaki, S. Samabhara, J. Katz, S. Gangappa⁎ Centers for Disease Control and Prevention, USA E-mail address: [email protected] (S. Gangappa)
B
Fig. 1. Change from baseline in specific IgGs after BB-12® (top) and L. casei 431® (bottom).
An increase of minimum two-fold in specific antibody levels was considered substantial2,3, and the number of subjects obtaining a substantial increase was significantly greater in both probiotic groups compared to placebo (Table 1). Table 1 Number of subjects with substantial increase* in specific plasma antibodies. Variable
Placebo Capsule (n = 48)
BB-12® Capsule (n = 53)
Placebo Drink (n = 54)
L. casei 431® Drink (n = 56)
Specific IgG (% of n) Specific IgG1 (% of n) Specific IgG3 (% of n)
20.8 8.3 4.2
81.1** 50.9** 66.0**
18.5 1.9 1.9
28.6 37.5** 46.4**
*Substantial increase = Increase (day 42-baseline) ≥ 2 x baseline. **p b 0.001 vs. placebo (Fisher's exact test).
Significantly greater Mean Fold Increases for vaccine-specific secretory IgA were observed in both probiotic groups compared to placebo (BB12®, p=0.017; L. casei 431®, p=0.035). Similar results were detected in total antibody concentrations. No differences were found for cytokines or innate immune parameters. Adverse event incidence and pattern was similar between groups, and tetanus-specific IgG did not change after the intervention indicating that supplementation with these probiotic strains only elicits antigen-specific immune responses.
Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. We investigated the influence of PEM on susceptibility and immune responses to influenza virus infection using a mouse model. Groups of weanling mice maintained on isocaloric diets providing varying levels of protein energy [18%, control diet containing adequate protein (AP), 5%/low protein (LP), and 2%/very low protein (VLP)] were infected with either pandemic 2009 H1N1 virus (A/Mexico/4108/ 2009) or laboratory-adapted H1N1 virus (A/PR/8/34) and assessed for disease severity and immune responsiveness. We found that, compared to mice fed with AP and LP diets, mice maintained on the VLP diet exhibited more severe disease following influenza infection based on the observed mortality and morbidity. Mice maintained on the VLP diet demonstrated diminished IFNγ levels and moderate increases in virus titer, in lung tissues, compared with mice on higher protein content diets. In addition, influenza virus infection resulted in diminished levels of inflammatory mediators in the lung tissue of mice maintained on the VLP diet. Furthermore, flow cytometric and histopathological analysis of lung tissue harvested from influenza virus-infected VLP-diet fed mice, when compared with mice on AP and LP-diets, showed an increase in trafficking of inflammatory cell types and expression of viral nucleoprotein (NP) antigen at day 6 postinfection. Moreover, groups of mice maintained on the VLP energy source showed a significantly lower hemagglutination inhibition antibody response and reduced total numbers of NP-specific CD8+ T cells compared with mice on higher protein content diets. Adoptive transfer of immune splenocytes from influenza infected mice maintained on VLP diet into naïve mice, when compared with transfer of cells from mice on AP and LP diets, resulted in an increase in virusinduced morbidity upon virus challenge. Taken together, our results highlight the impact of protein energy on immunity to influenza infection and suggest balanced protein energy replenishment may be a strategy to boost immunity against influenza infection. Keywords: Protein energy malnutrition, Influenza, Infection, Immunity doi:10.1016/j.ejphar.2011.09.201
Abstracts
milkdrink once daily for 6 weeks. Both probiotic products contained a minimum of one billion Colony Forming Units per dose. After two weeks subjects received an influenza vaccination. Plasma and saliva samples were collected at baseline and after 6 weeks for analysis of vaccinespecific and total antibodies, cytokines IL-2, IL-10 and INF-γ, and innate immune parameters. Results: The vaccine-specific antibody responses were significantly increased in both probiotic groups compared to their corresponding placebo group (Fig. 1).
A
Conclusions: Both probiotic strains increased the specific and total antibody response to an influenza vaccine. BB-12® and L. casei 431® may increase the body's resistance to common infections by strengthening both mucosal and systemic immunity. Keywords: Probiotics, Immune response, Vaccination, Clinical Trial References 1. Cummings, J.H., et al., 2004. PASSCLAIM – Gut health and immunity. Eur. J. Nutr. 43 (suppl 2), II/118–II/173. 2. Stepanova, L., et al., 2002. The humoral response to live and inactivated influenza vaccines administered alone and in combination to young adults and elderly. J. Clin. Virol. 24, 193–201. 3. Kurstak, E., 1985. Progress in enzyme immunoassays: production of reagents, experimental design, and interpretation. Bull. World Health Organ. 63, 793–811. doi:10.1016/j.ejphar.2011.09.200
Protein energy malnutrition decreases immunity and increases susceptibility to influenza infection A. Taylor, W. Cao, S. Zaki, S. Samabhara, J. Katz, S. Gangappa⁎ Centers for Disease Control and Prevention, USA E-mail address: [email protected] (S. Gangappa)
B
Fig. 1. Change from baseline in specific IgGs after BB-12® (top) and L. casei 431® (bottom).
An increase of minimum two-fold in specific antibody levels was considered substantial2,3, and the number of subjects obtaining a substantial increase was significantly greater in both probiotic groups compared to placebo (Table 1). Table 1 Number of subjects with substantial increase* in specific plasma antibodies. Variable
Placebo Capsule (n = 48)
BB-12® Capsule (n = 53)
Placebo Drink (n = 54)
L. casei 431® Drink (n = 56)
Specific IgG (% of n) Specific IgG1 (% of n) Specific IgG3 (% of n)
20.8 8.3 4.2
81.1** 50.9** 66.0**
18.5 1.9 1.9
28.6 37.5** 46.4**
*Substantial increase = Increase (day 42-baseline) ≥ 2 x baseline. **p b 0.001 vs. placebo (Fisher's exact test).
Significantly greater Mean Fold Increases for vaccine-specific secretory IgA were observed in both probiotic groups compared to placebo (BB12®, p=0.017; L. casei 431®, p=0.035). Similar results were detected in total antibody concentrations. No differences were found for cytokines or innate immune parameters. Adverse event incidence and pattern was similar between groups, and tetanus-specific IgG did not change after the intervention indicating that supplementation with these probiotic strains only elicits antigen-specific immune responses.
Protein energy malnutrition (PEM), a common cause of secondary immune deficiency in children, is associated with an increased risk of infections. We investigated the influence of PEM on susceptibility and immune responses to influenza virus infection using a mouse model. Groups of weanling mice maintained on isocaloric diets providing varying levels of protein energy [18%, control diet containing adequate protein (AP), 5%/low protein (LP), and 2%/very low protein (VLP)] were infected with either pandemic 2009 H1N1 virus (A/Mexico/4108/ 2009) or laboratory-adapted H1N1 virus (A/PR/8/34) and assessed for disease severity and immune responsiveness. We found that, compared to mice fed with AP and LP diets, mice maintained on the VLP diet exhibited more severe disease following influenza infection based on the observed mortality and morbidity. Mice maintained on the VLP diet demonstrated diminished IFNγ levels and moderate increases in virus titer, in lung tissues, compared with mice on higher protein content diets. In addition, influenza virus infection resulted in diminished levels of inflammatory mediators in the lung tissue of mice maintained on the VLP diet. Furthermore, flow cytometric and histopathological analysis of lung tissue harvested from influenza virus-infected VLP-diet fed mice, when compared with mice on AP and LP-diets, showed an increase in trafficking of inflammatory cell types and expression of viral nucleoprotein (NP) antigen at day 6 postinfection. Moreover, groups of mice maintained on the VLP energy source showed a significantly lower hemagglutination inhibition antibody response and reduced total numbers of NP-specific CD8+ T cells compared with mice on higher protein content diets. Adoptive transfer of immune splenocytes from influenza infected mice maintained on VLP diet into naïve mice, when compared with transfer of cells from mice on AP and LP diets, resulted in an increase in virusinduced morbidity upon virus challenge. Taken together, our results highlight the impact of protein energy on immunity to influenza infection and suggest balanced protein energy replenishment may be a strategy to boost immunity against influenza infection. Keywords: Protein energy malnutrition, Influenza, Infection, Immunity doi:10.1016/j.ejphar.2011.09.201