This could be the result of the internalization of LBP by cells of the innate immune system

This could be the result of the internalization of LBP by cells of the innate immune system. decreased levels of tissue inhibitor of metalloproteinases 4 (TIMP-4). Following treatment ofS. stercoralisinfection, the elevated levels of microbial translocation markers, acute-phase proteins, and inflammatory markers were all diminished. Our data thus show thatS. stercoralisinfection is characterized by microbial translocation and accompanying increases in levels of acute-phase proteins and markers of inflammation and provide data to suggest that microbial translocation Dihydroeponemycin is a feature of asymptomaticS. stercoralisinfection and is associated with an inflammatory response. KEYWORDS: microbial translocation markers, Strongyloides stercoralis, acute-phase proteins, inflammatory markers, proinflammatory cytokines == INTRODUCTION == Microbial translocation refers to the process by which the translocation of bacterial products results in elevated levels of lipopolysaccharide (LPS) in the circulation without overt bacteremia (1). LPS and 16S rRNA (common to most bacteria) are often used as indicators of bacterial translocation, and endotoxin core IgG antibody (EndoCAb) is also used as a surrogate marker for the measurement of circulating LPS levels (1, 2). iFABP may also reflect a breach in epithelial integrity associated with chronic intestinal infections (3). The prevalence of increased acute-phase protein concentrations during episodes of inflammation is used Dihydroeponemycin as a supporting prognostic and diagnostic tool for inflammatory gastrointestinal diseases (4). Matrix metalloproteinases (MMPs) and their endogenous inhibitor, tissue inhibitor of metalloproteinases 4 (TIMP-4), also play an important role in the process of tissue remodeling and destruction and can Dihydroeponemycin be detected in the sera of individuals with a variety of inflammatory disorders (5, 6). Heme oxygenase 1 (HO-1), a cytoprotective enzyme with anti-inflammatory and antioxidant properties, has been shown to play a fundamental role in the control of systemic inflammation (7). Microbial translocation is commonly observed under conditions associated with a disruption of the gastrointestinal (GI) epithelial barrier, such as inflammatory bowel disease, graft-versus-host disease, and chronic viral infections, including infections by human immunodeficiency computer virus (HIV) and hepatitis C virus (1, 2). Microbial translocation is also commonly associated with acute and chronic systemic immune activation and perturbations in T cell subset numbers (13, 8, 9). Although bacterial translocation is known to occur in infections affecting the integrity of the gut epithelium (10, 11), very few studies have examined the occurrence of this phenomenon in intestinal helminth infections. Among the common helminth parasites known to establish chronic infections in humans, Strongyloides stercoralis, the causative agent of strongyloidiasis (12), is unique in its ability to exist in free-living and autoinfective cycles (13, 14), with the latter allowing persistent long-lived infection. ChronicS. stercoralisinfection, although commonly clinically silent, can cause cutaneous, gastrointestinal, and/or pulmonary symptoms and, in the face of immune suppression, may present as hyperinfection syndrome or disseminated strongyloidiasis, conditions that are potentially fatal (15). To examine whether microbial translocation is a feature ofS. stercoralisinfection, we measured the circulating levels of bacterial translocation markers, acute-phase proteins, inflammatory markers (MMP-1, TIMP-4, and HO-1), and proinflammatory cytokines (interleukin-6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1], and macrophage inflammatory protein 1 [MIP-1]) inS. stercoralis-infected (INF) (before and after treatment) and uninfected (UN) individuals. Our data confirm the presence of microbial translocation and an associated acute-phase and proinflammatory response inS. stercoralisinfection and its reversal following therapy. == RESULTS == == S. stercoralisinfection is associated with elevated levels of LPS, sCD14, iFABP, and EndoCAb. == To determine the association of microbial translocation and related markers inS. stercoralisinfection, we measured the plasma levels of LPS, soluble CD14 (sCD14), iFABP, lipid-binding protein (LBP), and EndoCAb in INF and UN GU/RH-II individuals. As shown inFig. 1A, INF individuals had significantly higher levels of LPS (geometric mean [GM] of 0. 1141 endotoxin models [EU]/ml in INF versus 0. 06623 EU/ml in UN individuals; P= 0. 0005), sCD14 (GM of 21. 30 ng/ml in INF versus 14. 76 ng/ml in UN individuals; P= 0. 0204), and iFABP (GM of 0. 1258 ng/ml in INF versus 0. 06474 ng/ml in UN individuals; P= 0. 0384) than did UN individuals. Thus, S. stercoralisinfection is associated with elevated circulating levels of microbial translocation markers. == FIG 1 . == S. stercoralisinfection is associated with elevated levels of LPS, sCD14, iFABP, and EndoCAb. (A) Plasma levels of LPS, sCD14, iFABP, LBP, and EndoCAb inS. stercoralis-infected (n= 30) or uninfected (n= 28) individuals were measured by ELISAs. Data are shown as scatter plots, with bars representing the geometric means. Pvalues were calculated by.