Baseline iron status and presence of anaemia determine the course of systemic Salmonella infection following oral iron supplementation in mice.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health concern. However, preventive iron supplementation in regions with high burden of infectious diseases resulted in an increase of infection related morbidity and mortality. METHODS: We fed male C57BL/6N mice with either an iron deficient or an iron adequate diet. Next, they received oral iron supplementation or placebo followed by intraperitoneal infection with Salmonella Typhimurium (S.Tm). FINDINGS: We found that mice with IDA had a poorer clinical outcome than mice on an iron adequate diet. Interestingly, iron supplementation of IDA mice resulted in higher bacterial burden in organs and shortened survival. Increased transferrin saturation and non-transferrin bound iron in the circulation together with low expression of ferroportin facilitated the access of the pathogen to iron and promoted bacterial growth. Anaemia, independent of iron supplementation, was correlated with reduced neutrophil counts and cytotoxic T cells. With iron supplementation, anaemia additionally correlated with increased splenic levels of the cytokine IL-10, which is suggestive for a weakened immune control to S.Tm infection. INTERPRETATION: Supplementing iron to anaemic mice worsens the clinical course of bacterial infection. This can be traced back to increased iron delivery to bacteria along with an impaired anti-microbial immune response. Our findings may have important implications for iron supplementation strategies in areas with high endemic burden of infections, putting those individuals, who potentially profit most from iron supplementation for anaemia, at the highest risk for infections. FUNDING: Financial support by the Christian Doppler Laboratory for Iron Metabolism and Anemia Research.

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella typhimurium.

The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S. Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC. By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S. Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1ß and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S. Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression.

Salmonella enterica serovar enteritidis peritonitis with spontaneous intestinal perforation in an immunocompetent patient.

Few data reported non-typhoidal Salmonella peritonitis in immunocompromised patients. We reported the case of a man without immunosuppression or predisposing factor, who developed Salmonella enterica serovar Enteritidis peritonitis with spontaneous intestinal perforation. After emergent surgery, the patient was transferred to intensive care unit (ICU) because of respiratory, renal and haemodynamic failures. When S. enterica serovar Enteritidis was identified, antibiotics were de-escalated for ceftriaxone and metronidazole for 5 days. No immunosuppression was found. Evolution was favourable, and the patient has been discharged from the ICU on day 8. The originality of this case arises from a perforation peritonitis secondary to S. enterica without any immunosuppression. In absence of non-Typhi Salmonella data, we treated this patient as a typhoid perforation: surgical treatment, antibiotic association and supportive care.

Time Response of Oxidative/Nitrosative Stress and Inflammation in LPS-Induced Endotoxaemia-A Comparative Study of Mice and Rats.

Sepsis is a severe and multifactorial disease with a high mortality rate. It represents a strong inflammatory response to an infection and is associated with vascular inflammation and oxidative/nitrosative stress. Here, we studied the underlying time responses in the widely used lipopolysaccharide (LPS)-induced endotoxaemia model in mice and rats. LPS (10 mg/kg; from Salmonella Typhosa) was intraperitoneally injected into mice and rats. Animals of every species were divided into five groups and sacrificed at specific points in time (0, 3, 6, 9, 12 h). White blood cells (WBC) decreased significantly in both species after 3 h and partially recovered with time, whereas platelet decrease did not recover. Oxidative burst and iNOS-derived nitrosyl-iron hemoglobin (HbNO) increased with time (maxima at 9 or 12 h). Immune cell infiltration (CD68 and F4/80 content) showed an increase with time, which was supported by increased vascular mRNA expression of VCAM-1, P-selectin, IL-6 and TNF-α. We characterized the time responses of vascular inflammation and oxidative/nitrosative stress in LPS-induced endotoxaemic mice and rats. The results of this study will help to interpret and compare data from different animal species in LPS-induced endotoxaemia models for the identification of new drug targets.

Clinical-associated characteristics and microbiological features of bloodstream nontyphoidal salmonella infection in adult patients receiving allogeneic hematopoietic stem cell transplantation.

Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections. The median age at SCT was 35 years (interquartile range, 29-46) among the nine patients with bloodstream NTS infection. Male patients were predominant (78%). The median onset of bloodstream NTS infection was at 315 days after SCT (range, 207-629). Multivariate analysis revealed that extensive chronic graft-versus-host disease (GVHD) (OR 8.054, p = 0.003) and nonmyeloablative transplant conditioning (OR 4.604, p = 0.037) were significant associated characteristics for NTS infection. Currently, there are no published data analyzing and exploring post-transplant bloodstream NTS infections in adult allogeneic hematopoietic SCT. Our study determined the associated characteristics and microbiological features for this infection.

Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.

Sepsis is a deleterious inflammatory response to infection with high mortality. Reliable sepsis biomarkers could improve diagnosis, prognosis, and treatment. Integration of human genetics, patient metabolite and cytokine measurements, and testing in a mouse model demonstrate that the methionine salvage pathway is a regulator of sepsis that can accurately predict prognosis in patients. Pathway-based genome-wide association analysis of nontyphoidal Salmonella bacteremia showed a strong enrichment for single-nucleotide polymorphisms near the components of the methionine salvage pathway. Measurement of the pathway's substrate, methylthioadenosine (MTA), in two cohorts of sepsis patients demonstrated increased plasma MTA in nonsurvivors. Plasma MTA was correlated with levels of inflammatory cytokines, indicating that elevated MTA marks a subset of patients with excessive inflammation. A machine-learning model combining MTA and other variables yielded approximately 80% accuracy (area under the curve) in predicting death. Furthermore, mice infected with Salmonella had prolonged survival when MTA was administered before infection, suggesting that manipulating MTA levels could regulate the severity of the inflammatory response. Our results demonstrate how combining genetic data, biomolecule measurements, and animal models can shape our understanding of disease and lead to new biomarkers for patient stratification and potential therapeutic targeting.

Infection with Salmonella enterica Serovar Typhimurium Leads to Increased Proportions of F4/80+ Red Pulp Macrophages and Decreased Proportions of B and T Lymphocytes in the Spleen.

Infection of mice with Salmonella enterica serovar Typhimurium (Salmonella) causes systemic inflammatory disease and enlargement of the spleen (splenomegaly). Splenomegaly has been attributed to a general increase in the numbers of phagocytes, lymphocytes, as well as to the expansion of immature CD71+Ter119+ reticulocytes. The spleen is important for recycling senescent red blood cells (RBCs) and for the capture and eradication of blood-borne pathogens. Conservation of splenic tissue architecture, comprised of the white pulp (WP), marginal zone (MZ), and red pulp (RP) is essential for initiation of adaptive immune responses to captured pathogens. Using flow cytometry and four color immunofluorescence microscopy (IFM), we show that Salmonella-induced splenomegaly is characterized by drastic alterations of the splenic tissue architecture and cell population proportions, as well as in situ cell distributions. A major cause of splenomegaly appears to be the significant increase in immature RBC precursors and F4/80+ macrophages that are important for recycling of heme-associated iron. In contrast, the proportions of B220+, CD4+ and CD8+ lymphocytes, as well as MZ MOMA+ macrophages decrease significantly as infection progresses. Spleen tissue sections show visible tears and significantly altered tissue architecture with F4/80+ macrophages and RBCs expanding beyond the RP and taking over most of the spleen tissue. Additionally, F4/80+ macrophages actively phagocytose not only RBCs, but also lymphocytes, indicating that they may contribute to declining lymphocyte proportions during Salmonella infection. Understanding how these alterations of spleen microarchitecture impact the generation of adaptive immune responses to Salmonella has implications for understanding Salmonella pathogenesis and for the design of more effective Salmonella-based vaccines.

Direct ROS scavenging activity of CueP from Salmonella enterica serovar Typhimurium.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is an intracellular pathogen that has evolved to survive in the phagosome of macrophages. The periplasmic copper-binding protein CueP was initially known to confer copper resistance to S. Typhimurium. Crystal structure and biochemical studies on CueP revealed a putative copper binding site surrounded by the conserved cysteine and histidine residues. A recent study reported that CueP supplies copper ions to periplasmic Cu, Zn-superoxide dismutase (SodCII) at a low copper concentration and thus enables the sustained SodCII activity in the periplasm. In this study, we investigated the role of CueP in copper resistance at a high copper concentration. We observed that the survival of a cueP-deleted strain of Salmonella in macrophage phagosome was significantly reduced. Subsequent biochemical experiments revealed that CueP specifically mediates the reduction of copper ion using electrons released during the formation of the disulfide bond. We observed that the copper ion-mediated Fenton reaction in the presence of hydrogen peroxide was blocked by CueP. This study provides insight into how CueP confers copper resistance to S. Typhimurium in copper-rich environments such as the phagosome of macrophages.

Salmonella enterica serovar Minnesota urosepsis in a patient with Crohn's disease in the absence of recent or current gastrointestinal symptoms.

Salmonella enterica serovar Minnesota is a rarely isolated organism in clinical samples mainly grown from stool cultures. Sepsis due to Salmonella is known in severely immunocompromised patients, but so far urosepsis due to S. enterica serovar Minnesota has not been described. We report a case of a 31-year-old patient suffering from Crohn's disease treated with infliximab and azathioprine, in whom was implanted a double-J ureteric catheter for urolithiasis. The patient presented with urinary tract infection and severe sepsis. S. enterica serovar Minnesota was grown from urine and blood cultures. After empiric antimicrobial treatment with meropenem and vancomycin, treatment was changed to ceftriaxone. Antimicrobial treatment was continued for a total of 3 weeks without evidence of Salmonella recurrence on follow-up visits. Salmonella spp. rarely cause urinary tract infection and sepsis. However, in immunocompromised patients, non-typhoidal salmonellosis merits a thorough clinical and microbiological evaluation.

Diagnostic performance of serum interleukin-6 and interleukin-10 levels and clinical predictors in children with rotavirus and norovirus gastroenteritis.

OBJECTIVES: Rotavirus and norovirus are the two most common causes of acute viral gastroenteritis in children. This study aimed to explore the association of serum interleukin-6 (IL-6) and interleukin-10 (IL-10) levels and the clinical features in children with rotavirus and norovirus gastroenteritis. METHODS: This prospective study enrolled 168 acute gastroenteritis patients admitted to a tertiary care center. Peripheral blood samples were collected for IL-6 and IL-10 assays within the first 72 h of illness. The diagnostic performance of clinical tests was estimated using the receiver operating characteristic (ROC) analysis. Binary logistic regression modeling was performed to examine the predictive variables. RESULTS: Serum IL-6 and IL-10 were measured in children with rotavirus infection (n=30), norovirus infection (n=25), Salmonella infection (n=26), and in 11 healthy controls. There were significant higher degrees of severity of illness and levels of IL-10 in the rotavirus group as compared to the norovirus group. The binary logistic regression analysis revealed that both the ANC and maximum body temperature (BT) were significant clinical predictors for discriminating rotavirus and norovirus gastroenteritis. The ROC curve to evaluate the accuracy of logistic regression model had an AUC of 0.847 (95% CI: 0.741-0.952, p<0.001). CONCLUSIONS: IL-10 shows a significant discriminating ability between rotavirus and norovirus infection. A model incorporating maximum BT and ANC can help pediatricians to distinguish between rotavirus and norovirus in children with a suspected viral gastroenteritis.

Proteins derived from latex of C. procera maintain coagulation homeostasis in septic mice and exhibit thrombin- and plasmin-like activities.

The proteins derived from the latex (LP) of Calotropis procera are well known for their anti-inflammatory property. In view of their protective effect reported in the sepsis model, they were evaluated for their efficacy in maintaining coagulation homeostasis in sepsis. Intraperitoneal injection of LP markedly reduced the procoagulation and thrombocytopenia observed in mice infected with Salmonella; while in normal mice, LP produced a procoagulant effect. In order to understand its mechanism of action, the LP was subjected to ion-exchange chromatography, and the three subfractions (LPPI, LPPII, and LPPIII) thus obtained were tested for their proteolytic effect and thrombin- and plasmin-like activities in vitro. Of the three subfractions tested, LPPII and LPPIII exhibited proteolytic effect on azocasein and exhibited procoagulant effect on human plasma in a concentration-dependent manner. Like trypsin and plasmin, these subfractions produced both fibrinogenolytic and fibrinolytic effects that were mediated through the hydrolysis of the Aα, Bß, and γ chains of fibrinogen and α-polymer and γ-dimer of fibrin clot, respectively. This study shows that the cysteine proteases present in the latex of C. procera exhibit thrombin- and plasmin-like activities and suggests that these proteins have therapeutic potential in various conditions associated with coagulation abnormalities.

[Character of lipopolysaccharide-binding protein level changes in different pathological conditions and dysbiosis].

AIM: To evaluate diagnostic value of lipopolysaccharide-binding protein (LBP) level in different infectious processes and dysbiosis. MATERIALS AND METHODS: Serum samples of patients with salmonellosis, urogenital chlamydiosis, community-acquired pneumonia, polypous rhinosinusitis, and bacterial vaginosis were studied. RESULTS: LBP level were lower in patients with salmonellosis compared to healthy persons and decreased with increasing severity of the disease. Higher levels of LBP were detected in patients with chlamydiosis. Direct correlation between LBP level and etiology and severity of community-acquired pneumonia was demonstrated. In patients with polypous sinusitis, LBP level correlated directly with duration of disease, and inversely--with duration of remission. Twofold increase of mean LBP blood concentration and its correlation with duration of dysbiosis in patients with bacterial vaginosis were revealed. CONCLUSION: Multidirectional modulation of antiendotoxin defense was observed in different pathological conditions.

Cholinergic stimulation of the immune system protects against lethal infection by Salmonella enterica serovar Typhimurium.

SUMMARY: The cholinergic nervous system has been demonstrated to attenuate the inflammatory response during sepsis via the inhibitory action of acetylcholine (ACh) on macrophages. These findings were largely based on experimental sepsis models using endotoxin as the inducing agent. Herein, however, we report that the specific inhibition of acetylcholinesterase (AChE) renders animals more resistant to infection by a virulent strain of Salmonella enterica serovar Typhimurium, a Gram-negative enteric pathogen. Inhibition of AChE was induced by a subchronic exposure to paraoxon, a potent anti-cholinesterase metabolite of the organophosphorous compound parathion. Our findings indicate that inhibition of AChE enhanced survival of infected mice in a dose-dependent fashion and this correlated with efficient control of bacterial proliferation in target organs. Immunologically, inhibition of AChE enabled the animals to mount a more effective inflammatory anti-microbial response, and to secrete higher levels of interleukin-12, a key T helper type 1-promoting cytokine. The ACh-induced enhancement in resistance to infection was abrogated by co-administration of an oxime which can reactivate AChE. Hence, in a model of Gram-negative bacterial infection, cholinergic stimulation is shown to enhance the anti-microbial immune response leading to effective control of bacterial proliferation and enhanced animal survival.

Hemograma e perfil bioquímico sérico, inclusive hemogasométrico, de bezerros infectados experimentalmente com Salmonella Dublin / Blood cell counts and serum biochemical profile, including blood gas levels, in Salmonella Dublin-infected calves

O objetivo do estudo foi avaliar o hemograma e o perfil bioquímico sérico, inclusive hemogasométrico, de bezerros infectados experimentalmente com Salmonella Dublin. Foram utilizados 12 bezerros sadios da raça Holandesa com 10 a 15 dias de idade, distribuídos aleatoriamente em dois grupos experimentais: grupo-controle (n= 6) e grupo infectado com 10(8)UFC de Salmonella Dublin (n=6). Os bezerros foram submetidos ao exame físico diário, e as amostras de sangue foram coletadas minutos antes da inoculação (0h) e 24, 48, 72, 96, 120, 144 e 168h após a inoculação. Além do hemograma e das análises hemogasométricas, foram mensuradas as atividades séricas das enzimas aspartato aminotransferase (AST), fosfatase alcalina (ALP), creatina cinase (CK), gamaglutamiltransferase (GGT) e lactato desidrogenase (LDH), e os teores de albumina, bilirrubinas, cálcio total, cálcio ionizado, sódio, potássio, cloretos, creatinina, ferro, fibrinogênio, fósforo, glicose, magnésio, proteína totais e ureia. As principais alterações foram: redução das concentrações de albumina, ferro, glicose, magnésio e proteína total, aumento do teor de fibrinogênio, leucocitose e acidose metabólica e hiponatremia.

The blood cell counts and biochemical profile, including blood gas levels, were evaluated, in Salmonella Dublin-infected calves. Twelve healthy 10 to 15-day old Holstein calves were randomly allotted into two groups: control (n=6) and group orally infected with 10(8) CFU Salmonella Dublin (n=6). The calves were submitted to physical examination and the blood samples were taken just before the inoculation (0h) and at 24, 48, 72, 96, 120, 144, and 168h later. Besides, blood cell counts, blood gas levels, and the serum concentrations of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine kinase (CK), gammaglutamyltransferase (GGT), lactate desidrogenase (LDH), albumin, bilirubin, total calcium, ionic calcium, sodium, potassium, chlorides, creatinine, iron, fibrinogen, phosphorus, glucose, magnesium, total protein, and urea were measured. The main findings included decrease in albumin, iron, glucose, magnesium, and total protein concentrations, and increase in fibrinogen level, leukocytosis, metabolic acidosis, and hyponatremia.

SpvC is a Salmonella effector with phosphothreonine lyase activity on host mitogen-activated protein kinases.

SpvC is encoded by the Salmonella virulence plasmid. We have investigated the biochemical function of SpvC and the mechanism by which it is secreted by bacteria and translocated into infected macrophages. We constructed a strain carrying a deletion in spvC and showed that the strain is attenuated for systemic virulence in mice. SpvC can be secreted in vitro by either the SPI-1 or SPI-2 type III secretion systems. Cell biological and genetic experiments showed that translocation of the protein into the cytosol of macrophages by intracellular bacteria is dependent on the SPI-2 T3SS. Using antibodies specific to phospho-amino acids and mass spectrometry we demonstrate that SpvC has phosphothreonine lyase activity on full-length phospho-Erk (pErk) and a synthetic 13-amino-acid phospho-peptide containing the TXY motif. A Salmonella strain expressing spvC from a plasmid downregulated cytokine release from infected cells.

Hemophagocytic macrophages harbor Salmonella enterica during persistent infection.

Salmonella enterica subspecies can establish persistent, systemic infections in mammals, including human typhoid fever. Persistent S. enterica disease is characterized by an initial acute infection that develops into an asymptomatic chronic infection. During both the acute and persistent stages, the bacteria generally reside within professional phagocytes, usually macrophages. It is unclear how salmonellae can survive within macrophages, cells that evolved, in part, to destroy pathogens. Evidence is presented that during the establishment of persistent murine infection, macrophages that contain S. enterica serotype Typhimurium are hemophagocytic. Hemophagocytic macrophages are characterized by the ingestion of non-apoptotic cells of the hematopoietic lineage and are a clinical marker of typhoid fever as well as certain other infectious and genetic diseases. Cell culture assays were developed to evaluate bacterial survival in hemophagocytic macrophages. S. Typhimurium preferentially replicated in macrophages that pre-phagocytosed viable cells, but the bacteria were killed in macrophages that pre-phagocytosed beads or dead cells. These data suggest that during persistent infection hemophagocytic macrophages may provide S. Typhimurium with a survival niche.

Salmonelosis extraintestinal: clínica, epidemiología y resistencia antimicrobiana / Salmonella extraintestinal infection: clinic features, epidemiology and antimicrobial resistance

Se evaluaron retrospectivamente las características clínicas de 59 pacientes con aislamientos extraintestinales de Salmonella enterica no Typhi y la resistencia antibiótica entre 1988 y 2004. En el 95% de los casos se conocieron las condiciones de base del huésped que consistieron en: enfermedad oncohematológica (15), lupus eritematoso sistémico (11), síndrome de inmuno deficiencia adquirida (10), pacientes internados en neonatología (8), colecistitis (4) y otras (7). Las formas clínicas halladas fueron: bacteriemias primarias (26), bacteriemias secundarias a gastroenteritis (15), artritis séptica (7), infección urinaria (12), infección intraabdominal (5), meningitis (1) y pericarditis (1). En 29 pacientes se aisló Salmonella enterica no Typhi en más de una localización. El 15,8% y el 21,0% de 59 aislamientos presentaron resistencia a cefalosporinas de 3ª generación y a ampicilina, respectivamente. Salmonella Agona causó un brote epidémico en la sala de cuidados intensivos de neonatología, aislándose de sangre en 5 pacientes y en uno también de LCR. Este serotipo fue multirresistente. Imipenem, trimetroprima-sulfometoxazol y ciprofloxacina fueron los antibióticos más activos (CIM 50: 0,5; 0,5 y 0,002 µg/mL, respectivamente).

The clinical and antimicrobial resistance of 59 patients with extraintestinal infection by nontyphi Salmonella was retrospectively evaluated from 1988 to 2004. In 95% of the patients there were underlying diseases, which included: oncohematologic disease (15), systemic lupus erythematosus (11), acquired immunodeficiency disease (AIDS) (10), patients of neonatal units (8), colecistitis (4), and other disorders (7). The clinical manifestation were primary bacteremias (26), bacteremias secondary to gastroenteritis (15), arthritis (7), urinary tract infections (12), abdominal infections (5), meningitis (1) and pericarditis (1). In 29 patients Salmonella enterica no Typhi was isolated in more than one site. Resistance to third generation cephalosporins was observed in 15,8 % of these isolates, and resistance to ampicillin in 21,0%. Salmonella Agona was isolated from an outbreak in neonatal ICU; the organism was recovered from blood samples of five neonates and in one patient also isolated from CSF. These isolates showed multiresistance. Imipenem, trimetoprim-sulfametoxazol and ciprofloxacin were the three most active antimicrobial agents (MIC 50: 0.5, 0.5 and 0.002 µg/mL, respectively).

The diagnostic value of serum interleukins 6 and 8 in children with acute gastroenteritis.

OBJECTIVES: Early identification of the pathogen causing acute gastroenteritis in children helps the physicians managing the disease and prevents unnecessary antibiotic treatment. C-reactive protein (CRP), interleukin (IL) 6 and IL-8 play a major role in immune responses and have been studied in a large number of infectious and noninfectious inflammatory diseases. The purpose of this study was to determine the serum IL-6 and IL-8 concentrations early in the course of acute gastroenteritis to see if these cytokines were useful diagnostic markers in differentiating viral from bacterial gastroenteritis. METHODS: Interleukin 6, IL-8 and CRP were measured in 18 patients with bacterial gastroenteritis, 21 patients with viral gastroenteritis and 17 healthy children. RESULTS: Interleukin 6 and CRP concentrations in patients with bacterial gastroenteritis were significantly higher than those in patients with viral gastroenteritis and healthy controls (P < 0.001). IL-8 concentrations in patients with viral and bacterial gastroenteritis were both increased and were not statistically different. IL-6 and IL-8 levels had diagnostic sensitivities of 79% and 50% and specificities of 86% and 67%, respectively. The combination of IL-6 and CRP had a sensitivity of 94%, specificity of 71%, a positive predictive value of 74% and a negative predictive value of 93.75%. CONCLUSIONS: Serum IL-6 may be a useful marker for early differentiation of viral and bacterial gastroenteritis in children, especially in combination with CRP.

Serum levels of interferon-gamma, interleukin-12, tumour necrosis factor-alpha, and interleukin-10, and bacterial clearance in patients with gastroenteric Salmonella infection.

Cytokines as intercellular signal molecules are responsible to a great extent for the pathological processes in Salmonella infection, as well as for the development of protective mechanisms in the disease. The present study aimed to reveal the correlation between serum levels of IFN-gamma, IL-12, TNF-alpha and IL-10, measured by enzyme-immunoassay, and clearance of bacteria in stool of patients with gastroenteric Salmonella infection. The study included 36 patients with culture confirmed gastroenteric Salmonella infection. At discharge from hospital, 20 patients recovered with bacteriological negative stool culture for Salmonella and 16 were Salmonella excretors. Mean serum concentrations of IFN-gamma, IL-12, TNF-alpha and IL-10 in the acute stage were compared between the 2 groups of patients and with those of healthy controls. Serum levels of examined cytokines were increased (p<0.001) in the patients in comparison with the healthy controls. In patients with early bacterial clearance mean serum concentrations of IFN-gamma, IL-12 and TNF-alpha in the acute stage were significantly (p<0.05) higher than in the non-clearance group. IL-10 serum level showed an opposite correlation (p<0.01) and higher values in Salmonella excretors. The accumulated data imply that Th1 type cytokines probably participate in protective immunity and early bacterial clearance in patients with gastroenteric Salmonella infection.