Impact of interleukin-10, soluble CD25 and interferon-γ on the prognosis and early diagnosis of bacteremic systemic inflammatory response syndrome: a prospective observational study.

INTRODUCTION: The pathophysiology of sepsis consists of two phases. A first phase characterized by a substantial increase of pro-inflammatory mediators including cytokines and systemic inflammatory markers, and a second phase (immunoparalysis, immunodysregulation) associated with the rise of anti-inflammatory mediators. In this study we prospectively analyzed 52 consecutive patients with diagnosis of systemic inflammatory response syndrome (SIRS) at hospital admission to evaluate prognostic and early diagnostic performance of interleukin-10 (IL-10), soluble CD25 (sCD25) and interferon-γ (IFN-γ) and to confirm the prognostic accuracy of the sequential organ failure assessment (SOFA) score. METHODS: Patients were divided in two groups (group 1, n=28 patients with bacteremic SIRS and group 2, n=24 patients with non-bacteremic SIRS) and then stratified into survivors (n=39) and nonsurvivors (n=13). Serum markers were evaluated on the day of hospital admission (D-1) and on the 7th day of hospital stay (D-7). Concentration of sCD25 was evaluated by a sandwich ELISA kit. Levels of IL-10 and IFN-γ were quantified by a cytokine biochip array by the evidence investigator analyzer. Differences between groups were established by the Mann-Whitney test. Accuracy, sensitivity and specificity of diagnostic markers were evaluated by the receiver-operating characteristic curve analysis. Multivariate analysis was carried out to evaluate whether studied biomarkers are independent predictors of poor outcome in prognosis, and of bacteremic SIRS in diagnosis. RESULTS: IL-10, sCD25 and SOFA scores of survivors and nonsurvivors were significantly different both at D-1 (P=0.0014; P=0.014 and P=0.0311 respectively) and at D-7 (P=0.0002, P=0.014 and P=0.0012 respectively). Between the above groups IFN-γ level was significantly different only at D-7 (P=0.0013). Moreover IL-10 and sCD25 were significantly higher in bacteremic versus non-bacteremic SIRS patients at D-1 and at D-7 (P<0.05). IFN-γ values showed a significant decrease (P<0.05) in patients of group 1 only at D-7. The diagnostic accuracy of IL-10 and sCD25 was confirmed by the analysis of the AUROCC at D-1 and D-7 respectively. Multivariate analysis revealed that sCD25 and IL-10 are independent predictors of a poor outcome for our patients during the first day of hospital admission. CONCLUSIONS: IL-10 and sCD25 gave a significant contribution to prognostic evaluation and early diagnosis of bacteremic SIRS. SOFA score appeared to be a reliable prognostic tool in this subset of patients.

Procalcitonin neutralizes bacterial LPS and reduces LPS-induced cytokine release in human peripheral blood mononuclear cells.

BACKGROUND: Procalcitonin (PCT) is a polypeptide with several cationic aminoacids in its chemical structure and it is a well known marker of sepsis. It is now emerging that PCT might exhibit some anti-inflammatory effects. The present study, based on the evaluation of the in vitro interaction between PCT and bacterial lipopolisaccharide (LPS), reports new data supporting the interesting and potentially useful anti-inflammatory activity of PCT. RESULTS: PCT significantly decreased (p < 0.05) the limulus amoebocyte lysate (LAL) assay reactivity of LPS from both Salmonella typhimurium (rough chemotype) and Escherichia coli (smooth chemotype). Subsequently, the in vitro effects of PCT on LPS-induced cytokine release were studied in human peripheral blood mononuclear cells (PBMC). When LPS was pre-incubated for 30 minutes with different concentrations of PCT, the release of interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFα) by PBMC decreased in a concentration-dependent manner after 24 hours for IL-10 and 4 hours for TNFα. The release of monocyte chemotactic protein-1 (MCP-1) exhibited a drastic reduction at 4 hours for all the PCT concentrations assessed, whereas such decrease was concentration-dependent after 24 hours. CONCLUSIONS: This study provides the first evidence of the capability of PCT to directly neutralize bacterial LPS, thus leading to a reduction of its major inflammatory mediators.

The Janus face of Bartonella quintana recognition by Toll-like receptors (TLRs): a review.

Bartonella quintana (B. quintana) is a facultative, intracellular bacterium, which causes trench fever, chronic bacteraemia and bacillary angiomatosis. Little is known about the recognition of B. quintana by the innate immune system. In this review, we address the impact of Toll-like receptors (TLRs) on the recognition of B. quintana and the activation of the host defense. When experimental models using human mononuclear cells, transfected CHO cells, or TLR2-/- and TLR4-/- mice were used, differential effects of TLR2 and TLR4 have been observed. B. quintana micro-organisms stimulated cytokine production through TLR2-mediated signals, whereas no role for TLR4 in the recognition of this pathogen was observed. When single, water-phenol extraction was performed, B. quintana LPS, stimulated cytokine production in a TLR2-dependent manner. However, when double extraction was performed in order to generate highly purified LPS, B. quintana LPS entirely lost its capacity to stimulate cytokines, demonstrating that non-LPS components of B. quintana are responsible for the recognition through TLR2. Moreover, B. quintana LPS was shown to be a potent antagonist of Toll-like receptor 4 (TLR4). In conclusion, B. quintana is an inducer of cytokines through TLR2-, but not TLR4-, dependent mechanisms. This stimulation is induced by bacterial components other than lipopolysaccharide. B. quintana LPS is a naturally occurring antagonist of Toll-like receptor 4 (TLR4). In view of the role played by TLR4 in inflammation, B. quintana LPS may be useful as an anti-TLR4 agent with therapeutic potential in both infections and autoimmune inflammation.

Ascaris lumbricoides-induced suppression of total and specific IgE responses in atopic subjects is interleukin 10-independent and associated with an increase of CD25(+) cells.

Ascaris presence in humans has been associated with high levels of blood eosinophils and serum IgE. This study was designed to address the influence of Ascaris infection on allergic and inflammatory parameters of atopic subjects. A cross-sectional design was used, and atopic individuals to be assessed were divided into 3 groups including Ascaris-infected, anti-Ascaris IgG-positive (seropositive), and control subjects. All subjects enrolled had positive skin test reactivity to at least 1 perennial or seasonal allergen; however, levels of C-reactive protein, C3, and C4 were within normal range values. Eosinophil percentage was not significantly different among the groups studied. Total IgE and specific anti-Ascaris IgE levels in the seropositive group were significantly higher than concentrations found in both control and infected groups. Interleukin (IL)-4 release in Ascaris-infected patients was significantly increased versus seropositives, who were able to produce more IL-4 than controls. The levels of IL-10 were lower in the seropositives as well as infected subjects in comparison with controls. CD25(+) lymphocyte populations were significantly increased in the infected group versus the seropositives as well as the controls. Lung function tests of some selected seropositive subjects were significantly impaired. The same parameters of a representative infected patient were not different from controls. Our data on T helper type 2 cells (Th2) and regulatory T cells (Treg) features, as well as CD25(+) lymphocyte increase, suggest an Ascaris-induced mechanism leading to parasite survival. Moreover, the stable control of both T helper type 1 cells (Th1) and Th2 immunity cascades, paralleled by the absence of overwhelming inflammatory systemic reactions and lack of allergic syndromes, may result in a favorable host condition.