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Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

Anuradha R, George PJ, Pavan Kumar N, Fay MP, Kumaraswami V, Nutman TB, Babu S - PLoS Pathog. (2012)

Bottom Line: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis.Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India.

ABSTRACT
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag-) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag- compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

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Related in: MedlinePlus

Correlation between circulating microbial products and inflammatory cytokines in filarial infected individuals.(A) Plasma levels of LPS were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. (B) Plasma levels of LBP were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. P and r values were calculated using the Spearman Rank correlation test. Data are shown as scatter plots with the circles representing INF and the triangles representing CP Ag+ individuals.
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ppat-1002749-g004: Correlation between circulating microbial products and inflammatory cytokines in filarial infected individuals.(A) Plasma levels of LPS were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. (B) Plasma levels of LBP were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. P and r values were calculated using the Spearman Rank correlation test. Data are shown as scatter plots with the circles representing INF and the triangles representing CP Ag+ individuals.

Mentions: The relationships between the levels of LPS and/or LBP levels and plasma cytokines were next assessed (figure 4). As shown in figure 4A, levels of LPS exhibited a highly significant positive correlation with the plasma levels of IL-1β (r = 0.4942; P<0.001), IL-12 (r = 0.4802; P<0.0001), and TNF-α (r = 0.4494; P<0.0001) in all actively infected individuals. Conversely, LBP levels were significantly negatively correlated with the plasma levels of IL-12 (r = −0.3255; P = 0.0005) (figure 4B). Thus, the process by which microbial translocation occurs appears to be significantly associated with the pro-inflammatory cytokine levels in filarial infection.


Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.

Anuradha R, George PJ, Pavan Kumar N, Fay MP, Kumaraswami V, Nutman TB, Babu S - PLoS Pathog. (2012)

Correlation between circulating microbial products and inflammatory cytokines in filarial infected individuals.(A) Plasma levels of LPS were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. (B) Plasma levels of LBP were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. P and r values were calculated using the Spearman Rank correlation test. Data are shown as scatter plots with the circles representing INF and the triangles representing CP Ag+ individuals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369944&req=5

ppat-1002749-g004: Correlation between circulating microbial products and inflammatory cytokines in filarial infected individuals.(A) Plasma levels of LPS were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. (B) Plasma levels of LBP were correlated with the levels of IL-1β, IL-6, IL-12 and TNF-α from individuals with active infection [CP Ag+ and INF (n = 108–112)]. P and r values were calculated using the Spearman Rank correlation test. Data are shown as scatter plots with the circles representing INF and the triangles representing CP Ag+ individuals.
Mentions: The relationships between the levels of LPS and/or LBP levels and plasma cytokines were next assessed (figure 4). As shown in figure 4A, levels of LPS exhibited a highly significant positive correlation with the plasma levels of IL-1β (r = 0.4942; P<0.001), IL-12 (r = 0.4802; P<0.0001), and TNF-α (r = 0.4494; P<0.0001) in all actively infected individuals. Conversely, LBP levels were significantly negatively correlated with the plasma levels of IL-12 (r = −0.3255; P = 0.0005) (figure 4B). Thus, the process by which microbial translocation occurs appears to be significantly associated with the pro-inflammatory cytokine levels in filarial infection.

Bottom Line: Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients.Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis.Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers.

View Article: PubMed Central - PubMed

Affiliation: National Institutes of Health, International Center for Excellence in Research, Chennai, India.

ABSTRACT
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag-) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag- compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.

Show MeSH
Related in: MedlinePlus