Coronavirus Disease 2019 in Autoimmune Hepatitis: A Lesson From Immunosuppressed Patients.

Chronic immunosuppression is associated with increased and more severe viral infections. However, little is known about the association between immunosuppression and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our aim was to describe the clinical course of patients with immunosuppressed autoimmune hepatitis (AIH) during coronavirus disease 2019 (COVID-19) infection in Italy. Our study is a case series of patients with AIH treated with immunosuppression, who tested positive for SARS-CoV-2 in March 2020 during the outbreak of COVID-19. Ten patients from seven different hospitals in Italy were diagnosed with COVID-19 during the outbreak of SARS-CoV-2 in March 2020. Seven subjects were female (70%), and age ranged from 27 to 73 years. Before the onset of SARS-CoV-2 infection, all patients were taking immunosuppressive therapy for AIH, and eight of them were on biochemical remission. Two other patients had recent acute onset of their AIH, and consequently started high-dose steroids, as per induction protocol. All patients had a respiratory syndrome and a positive nasal swab for SARS-CoV-2. Five patients developed a computed tomography-confirmed COVID-19 pneumonia. Six subjects received a combination of antiretroviral and antimalarial drugs. In seven patients, the dosage of immunosuppressive medication was changed. Liver enzymes were repeated during SARS-CoV-2 infection in all hospitalized cases; they remained within the normal range in all cases, and improved in the two acute cases treated with high-dose steroids. The clinical outcome was comparable to the reported cases occurring in non-immunosuppressed subjects. Conclusion: Patients under immunosuppressive therapy for AIH developing COVID-19 show a disease course presumptively similar to that reported in the non-immunosuppressed population. These data might aid in medical decisions when dealing with SARS-CoV-2 infection in immunocompromised patients.

New light on ancient enzymes - in vitro CO2 Fixation by Pyruvate Synthase of Desulfovibrio africanus and Sulfolobus acidocaldarius.

Two variants of the enzyme family pyruvate:ferredoxin oxidoreductase (PFOR), derived from the anaerobic sulfate-reducing bacterium Desulfovibrio africanus and the extremophilic crenarchaeon Sulfolobus acidocaldarius, respectively, were evaluated for their capacity to fixate CO2 in vitro. PFOR reversibly catalyzes the conversion of acetyl-CoA and CO2 to pyruvate using ferredoxin as redox partner. The oxidative decarboxylation of pyruvate is thermodynamically strongly favored, and most previous studies only considered the oxidative direction of the enzyme. To assay the pyruvate synthase function of PFOR during reductive carboxylation of acetyl-CoA is more challenging and requires to maintain the reaction far from equilibrium. For this purpose, a biochemical assay was established where low-potential electrons were introduced by photochemical reduction of EDTA/deazaflavin and the generated pyruvate was trapped by chemical derivatization with semicarbazide. The product of CO2 fixation could be detected as pyruvate semicarbazone by HPLC-MS. In a combinatorial approach, both PFORs were tested with ferredoxins from different sources. The pyruvate semicarbazone product could be detected with low-potential ferredoxins of the green sulfur bacterium Chlorobium tepidum and of S. acidocaldarius whereas CO2 fixation was not supported by the native ferredoxin of D. africanus. Methylviologen as an artificial electron carrier also allowed CO2 fixation. For both enzymes, the results are the first demonstration of CO2 fixation in vitro. Both enzymes exhibited high stability in the presence of oxygen during purification and storage. In conclusion, the employed PFOR enzymes in combination with non-native ferredoxin cofactors might be promising candidates for further incorporation in biocatalytic CO2 conversion. ENZYMES: EC1.2.7.1. Pyruvate:Ferredoxin Oxidoreductase.

Point shear-wave elastography in chronic pancreatitis: A promising tool for staging disease severity.

BACKGROUND: Objectives: ElastPQ®-pSWE is an ultrasound technique developed to stage disease severity in patients with chronic liver diseases. Little data is available about its application to the pancreas. We aimed to assess the feasibility and reproducibility of pancreatic stiffness (PS) measurements in patients with chronic pancreatitis and their relationship with clinical and laboratory data. MATERIAL AND METHODS: 52 consecutive patients with chronic pancreatitis (CP) (40 males; median age 60 years) underwent hepatic and pancreatic pSWE. Liver stiffness was measured by transient elastography, 42 healthy subjects being controls (25 males; median age 54 years). Pancreatic pSWE inter-observer agreement was analyzed by intraclass correlation coefficient (ICC). The effects of clinical, laboratory and US data on PS measurements were evaluated by linear regression. RESULTS: pSWE was feasible in all the CP patients, but one. Pancreatic stiffness was significantly higher in CP patients than healthy controls (4.3 ± SD 2.4 vs. 2.8 ± SD 1.1 kPa, respectively, p = 0.001). Significantly higher values in the CP group were observed in patients with longer disease duration (>10 vs. ≤10 years) (5.8 ± SD 4 vs. 3.9 ± SD 1.5 kPa, respectively, p = 0.01), on chronic analgesic drugs (6.0 vs. 3.5 kPa, p < 0.05) and with lower body weight (p < 0.05, r = -0.38). At multivariate analysis all the three variables resulted independently associated to the pancreatic stiffness value. The ICC for PS was 0.77. CONCLUSIONS: ElastPQ®-pSWE is promising and reproducible in assessing pancreatic stiffness, which mainly reflects disease length and severity. Accordingly, its use is of potential value in stratifying CP patients by identifying those with a more serious degree of disease.

Mood disorders and non-celiac gluten sensitivity.

The association between gluten related disorders and psychiatric diseases has been firmly demonstrated. Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients responsive to gluten-free diet after ruling out celiac disease and wheat allergy. The pathogenesis of neuro-psychiatric disorders in NCGS is unclear. An association between gluten and schizophrenia was described for the first time in 1950 by Bender et al. In the 1950's, Dicke noted that gluten-free diet improved mood in celiac patients. In 1970, Goldberg et al., in a study of 80 celiac patients, found that 34% of them showed minor affective disorders. Bipolar disorder patients show an increase of blood anti gliadin deamidated antibodies (IgG). The effect of diet and nutrition on autistic spectrum disorders has been investigated in the last two decades, particularly focusing on the symptoms of hyperactivity and attention. Toxoplasma gondii and other neurotropic pathogens as Influenzavirus and Coronavirus may be associated with mood disorders, probably secondary to an increased intestinal permeability. Abnormalities of host-microbiota interactions or of gut-microbiota composition have been associated with central nervous system disorders, such as autism, anxiety, depression and the integrity of intestinal microbiota may be considered a potential therapeutic goal to treat these conditions.

Bowel ultrasound imaging in patients with cystic fibrosis: Relationship with clinical symptoms and CFTR genotype.

BACKGROUND: Ultrasound imaging is used to assess bowel abnormalities in gastrointestinal diseases. We aimed to assess the rate of predefined bowel ultrasound signs and their relationship with gastrointestinal symptoms and the cystic fibrosis transmembrane conductance regulator (CFTR) genotype in cystic fibrosis patients in regular follow-up. METHODS: Prospective study of 70 consecutive patients with cystic fibrosis and 45 controls who underwent abdominal ultrasound; pertinent findings were related to gastrointestinal symptoms and, in cystic fibrosis patients, to pancreatic status, malabsorption degree, lipase intake, CFTR genotype (classified as severe or mild against functional class of CFTR mutations). RESULTS: 96% patients showed at least one abnormal bowel ultrasound sign. Most frequent signs were lymph node enlargement (64%), bowel loop dilatation (55%), thick corpuscular intraluminal content (49%), bowel wall hypervascularization (26%), thickened bowel wall (22%) and intussusception (17%). Patients with recurrent abdominal pain showed more bowel wall hypervascularization than patients without recurrent pain (47% vs. 19%, respectively; p = 0.02) and intussusception (58% vs. 17%, respectively; p < 0.01). Genotype was not associated to specific bowel ultrasound signs. Patients with bowel loop intussusception showed greater lipase intake than those without intussusception (8.118 ± 2.083 vs. 5.994 ± 4.187, respectively; p < 0.01). CONCLUSION: Cystic fibrosis patients present a higher rate of bowel ultrasound abnormalities than controls. Bowel ultrasound abnormalities are associated with abdominal symptoms.

Distinct mechanisms contribute to immunity in the lantibiotic NAI-107 producer strain Microbispora ATCC PTA-5024.

The investigation of self-resistance in antibiotic producers is important to understand the emergence of antibiotic resistance in pathogens and to improve antibiotic production. Lantibiotics are ribosomally synthesized antibiotics that mostly target peptidoglycan biosynthesis. The actinomycete Microbispora ATCC PTA-5024 produces the lantibiotic NAI-107, which interferes with peptidoglycan biosynthesis by binding bactoprenol-pyrophosphate-coupled peptidoglycan precursors. In order to understand how Microbispora counteracts the action of its own antibiotic, its peptidoglycan composition was analysed in detail. Microbispora peptidoglycan consists of muropeptides with D-Ala and Gly in similar proportion at the fourth position of the peptide stems and alternative 3-3 cross-links besides the classical 4-3 cross-links. In addition, the NAI-107 biosynthetic gene cluster (mlb) was analysed for the expression of immunity proteins. We show that distinct immunity determinants are encoded in the mlb cluster: the ABC transporter MlbYZ acting cooperatively with the transmembrane protein MlbJ and the lipoprotein MlbQ. NMR structural analysis of MlbQ revealed a hydrophobic surface patch, which is proposed to bind the cognate lantibiotic. This study demonstrates that immunity in Microbispora is not only based on one determinant but on the action of the distinct immunity proteins MlbQ, MlbYZ and MlbJ.

[Health issues and regulatory aspects of the use of ultrasound in physiotherapy]. / Problematiche sanitarie e aspetti normativi dell'utilizzo degli ultrasuoni in fisioterapia.

The use of ultrasounds in medicine requires, like all physical agents potentially harmful to human health, an accurate assessment of the risks to the health of patients. The nature and extent of these risks depend on exposure levels which in turn are differentiated according to the specific diagnostic or therapeutic applications. Intermediate exposure levels are associated to physiotherapic applications. To analyze specific issues relating to the effectiveness and safety of physiotherapic treatments, a review of the scientific literature and technical standards was carried out. At present, the actual effectiveness of ultrasound physiotherapy is still far from being clearly assessed: further clinical and experimental studies are needed in order to optimize therapies, determining the benefits and risks of treatments and deepening the understanding of the action mechanisms of the physical agent, even on the basis of a better characterization of those physical quantities mostly significant for biological effects. The examination of technical standards defining the security requirements of the equipment allowed the identification of some critical issues; on these bases some proposals are suggested for the improvement of quality and safety of treatments.

Self-resistance mechanisms of actinomycetes producing lipid II-targeting antibiotics.

Glycopeptides and several lantibiotics are lipid II-targeting antibiotics produced by actinomycetes. To protect themselves from their own product, antibiotic producers developed self-resistance mechanisms. Inspection of different producer strains revealed that their resistance is not only based on a single determinant but on the synergistic action of different factors. Glycopeptide producers possess different ways to synthesize a modified peptidoglycan to prevent the binding of the glycopeptide antibiotic. One possible modification is the synthesis of peptidoglycan precursors terminating with a D-alanyl-D-lactate (D-Ala-D-Lac) rather than with a D-alanyl-D-alanine (D-Ala-D-Ala) resulting in a 1000-fold decreased binding affinity of the glycopeptide to its target. The reprogramming of the peptidoglycan precursor biosynthesis is based on the action of VanHAX or paralogous enzymes as it was shown for Amycolatopsis balhimycina. A second peptidoglycan modification resulting in glycopeptide resistance was investigated in the glycopeptide A40926 producer Nonomuraea ATCC 39727. Nonomuraea eliminates the glycopeptide target by synthesizing a peptidoglycan with 3-3 cross-linked peptide stems. The carboxypeptidase VanYn provides tetrapeptides which serve as substrates for the L,D-transpeptidase catalyzing the formation of 3-3 cross-links. The occurrence of 3-3 cross-linked dimers is also an important feature of the lantibiotic NAI-107 producer Microbispora ATCC PTA-5024. Moreover, the D-Ala in the fourth position in the acceptor peptide of muropeptides is exchanged to glycine or serine in Microbispora, a side reaction of the L,D-transpeptidase. Together with the lipoprotein MlbQ, the ABC transporter MlbYZ and the transmembrane protein MlbJ it might contribute to the self-resistance in Microbispora ATCC PTA-5024.

The influence of illness severity on health satisfaction in patients with cardiovascular disease: the mediating role of illness perception and self-efficacy beliefs.

The importance of psychological factors in improving conditions of cardiovascular disease (CVD) patients is stressed by the guidelines for their prevention and rehabilitation, but little is known about the impact of illness severity on patients' well-being, and on the psychosocial variables that may mediate this association. The aim of this study was to investigate the role of illness perception and self-efficacy beliefs on the relationship between illness severity and health satisfaction in 75 CVD patients undergoing rehabilitation (80% men; mean age = 65.44) at the St. Luca Hospital, Istituto Auxologico Italiano, Milan, Italy. Illness severity was measured in terms of left ventricular ejection fraction; psychological factors were assessed at the beginning and end of rehabilitation. Results from path analyses showed that the relationships among CVD severity and health satisfaction were mediated by illness perception and self-efficacy beliefs. Findings underscored the importance of considering illness representations and self-efficacy beliefs to improve well-being in CVD patients.

Draft Genome Sequence of the Microbispora sp. Strain ATCC-PTA-5024, Producing the Lantibiotic NAI-107.

We report the draft genome sequence of Microbispora sp. strain ATCC-PTA-5024, a soil isolate that produces NAI-107, a new lantibiotic with the potential to treat life-threatening infections caused by multidrug-resistant Gram-positive pathogens. The draft genome of strain Microbispora sp. ATCC-PTA-5024 consists of 8,543,819 bp, with a 71.2% G+C content and 7,860 protein-coding genes.

Comparative study of ZnO and TiO2 nanoparticles: physicochemical characterisation and toxicological effects on human colon carcinoma cells.

Despite human gastrointestinal exposure to nanoparticles (NPs), data on NPs toxicity in intestinal cells are quite scanty. In this study we evaluated the toxicity induced by zinc oxide (ZnO) and titanium dioxide (TiO2) NPs on Caco-2 cells. Only ZnO NPs produced significant cytotoxicity, evaluated by two different assays. The presence of foetal calf serum in culture medium significantly reduced ZnO NPs toxicity as well as ion leakage and NP-cell interaction. The two NPs increased the intracellular amount of reactive oxygen species (ROS) after 6 h treatment. However, only ZnO NPs increased ROS and induced IL-8 release both after 6 and 24 h. Experimental data indicate a main role of chemical composition and solubility in ZnO NPs toxicity. Moreover our results suggest a key role of oxidative stress in ZnO NPs cytotoxicity induction related both to ion leakage and to cell interaction with NPs in serum-free medium.

The accuracy of noninvasive methods in the prediction of clinically relevant outcomes in patients with chronic liver disease.

The prognosis of chronic liver diseases, which represent a major public health problem, is mainly linked to the extent and progression of liver fibrosis and the subsequent risk of developing cirrhosis and related complications, mainly hepatocellular carcinoma. The article reviewed here reports on the prognostic role of liver stiffness as measured by transient elastography and other noninvasive methods in the prediction of clinical decompensation and hepatocellular carcinoma in patients with chronic hepatitis B. From the results of the study, liver stiffness measurement, as obtained using transient elastography and other noninvasive tests used to assess liver fibrosis, can accurately predict the development of hepatocellular carcinoma and variceal bleeding in patients with chronic hepatitis B.

The genus Actinoallomurus and some of its metabolites.

In the search for novel antibiotics, natural products continue to represent a valid source of bioactive molecules. During a program aimed at identifying previously unreported taxa of actinomycetes as potential source of novel compounds, we isolated hundreds of different representatives of a new group, initially designated as 'Alpha' and independently described as Actinoallomurus. We report on a PCR-specific method for the detection of this taxon, on appropriate growth conditions and on a pilot-screening program on 78 strains. The strains produce antibacterial or antifungal compounds at a relatively high frequency. Four strains were characterized in further detail: one produced the aromatic polyketide benanomicin B and its dexylosyl derivative; a second strain produced N-butylbenzenesulfonamide; a third strain was an efficient converter of soymeal isoflavonoids from soymeal constituents; and a fourth strain produced several coumermycin-related aminocoumarins, with coumermycin A2 as the major peak, and with some new congeners as minor components of the complex. These data suggest that Actinoallomurus strains possess several pathways for secondary metabolism and represent an attractive source in the search for novel antibiotics.

Determinants of the proinflammatory action of ambient particulate matter in immortalized murine macrophages.

BACKGROUND: Proximity to traffic-related pollution has been associated with poor respiratory health in adults and children. OBJECTIVES: We wished to test the hypothesis that particulate matter (PM) from high-traffic sites would display an enhanced capacity to elicit inflammation. METHODS: We examined the inflammatory potential of coarse [2.5-10 µm in aerodynamic diameter (PM(2.5-10))] and fine [0.1-2.5 µm in aerodynamic diameter (PM(0.1-2.5))] PM collected from nine sites throughout Europe with contrasting traffic contributions. We incubated murine monocytic-macrophagic RAW264.7 cells with PM samples from these sites (20 or 60 µg/cm²) and quantified their capacity to stimulate the release of arachidonic acid (AA) or the production of interleukin-6 and tumor necrosis factor-α (TNFα) as measures of their inflammatory potential. Responses were then related to PM composition: metals, hydrocarbons, anions/cations, and endotoxin content. RESULTS: Inflammatory responses to ambient PM varied markedly on an equal mass basis, with PM(2.5-10) displaying the largest signals and contrasts among sites. Notably, we found no evidence of enhanced inflammatory potential at high-traffic sites and observed some of the largest responses at sites distant from traffic. Correlation analyses indicated that much of the sample-to-sample contrast in the proinflammatory response was related to the content of endotoxin and transition metals (especially iron and copper) in PM(2.5-10). Use of the metal chelator diethylene triamine pentaacetic acid inhibited AA release, whereas recombinant endotoxin-neutralizing protein partially inhibited TNFα production, demonstrating that different PM components triggered inflammatory responses through separate pathways. CONCLUSIONS: We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells.

Exposure to ZnO nanoparticles induces oxidative stress and cytotoxicity in human colon carcinoma cells.

Engineered nanoparticles offer great promise in many industrial and biomedical applications, however little information is available about gastrointestinal toxicity. The purpose of this study was to assess the cytotoxicity, oxidative stress, apoptosis and proinflammatory mediator release induced by ZnO nanoparticles on human colon carcinoma LoVo cells. The biological activity of these particles was related to their physico-chemical characteristics. The physico-chemical characteristics were evaluated by analytical electron microscopy. The cytotoxicity was determined by growth curves and water-soluble tetrazolium assay. The reactive oxygen species production, cellular glutathione content, changes of mitochondrial membrane potential and apoptosis cell death were quantified by flow cytometry. The inflammatory cytokines were evaluated by enzyme-linked immunoadsorbent assay. Treatment with ZnO (5µg/cm(2) corresponding to 11.5µg/ml) for 24h induced on LoVo cells a significant decrease of cell viability, H2O2/OH increase, O2(-) and GSH decrease, depolarization of inner mitochondrial membranes, apoptosis and IL-8 release. Higher doses induced about 98% of cytotoxicity already after 24h of treatment. The experimental data show that oxidative stress may be a key route in inducing the cytotoxicity of ZnO nanoparticles in colon carcinoma cells. Moreover, the study of the relationship between toxicological effects and physico-chemical characteristics of particles suggests that surface area does not play a primary role in the cytotoxicity.

Transient elastography assessment of the liver stiffness dynamics during acute hepatitis B.

BACKGROUND AND AIMS: The diagnostic accuracy of transient elastography (TE) for assessment of hepatic fibrosis is hampered by several factors, including acute parenchymal injury. Evaluation of liver stiffness (LS) using TE during acute hepatitis B may help to assess chronic hepatitis B patients with flares. PATIENTS AND METHODS: Twelve patients consecutively referred for acute hepatitis B, underwent sequential examinations with TE and laboratory examinations for 24 weeks. RESULTS: On admission, aminotransferase ranged from 487 to 6067 IU/l (median=2590 IU/l) and LS ranged from 7.1 to 57 kPa (median=15.6 kPa) with nine (75%) patients showing LS greater than 11.9 kPa, that is, the predictive cutoff for cirrhosis. LS levels correlated significantly with bilirubin, only (r=0.58, P<0.05). During follow-up, LS declined from 15.6 to 5.2 kPa at week 24, with a significant reduction being observed at week 2 for aminotransferase (from 2590 to 452 IU/l, P<0.0001) and at week 6 for both LS (from 15.6 to 6.0 kPa, P=0.008) and bilirubin (from 10.7 to 0.95 mg/dl, P<0.01). Median decline of LS significantly correlated with bilirubin decline (rs=0.70, P<0.05). At week 24, 10 (83%) patients showed LS of less than 7.9 kPa and two (17%) patients had LS values between 7.9 and 11.9 kPa, including the only patient who developed chronic hepatitis B. CONCLUSION: In patients with acute hepatitis B, the initial high values of LS mimicking LS cutoff of cirrhosis, likely reflect the liver cell inflammation, oedema and swelling as they progressively taper down during hepatitis resolution.

Winter urban air particles from Rome (Italy): effects on the monocytic-macrophagic RAW 264.7 cell line.

Epidemiological data show an association between exposure to elevated levels of particulate matter (PM), in particular the fine fraction (<2.5 microm in diameter), and an increase in cardiovascular mortality and respiratory symptoms. The aim of this study was to compare the in vitro toxicity of coarse and fine particulate matter collected with a cascade impactor during winter in an urban area of Rome in relation to their physicochemical characterization (size distribution and chemical composition) as assessed by analytical electron microscopy (SEM/EDX). The X-ray microanalysis data of single particles of coarse and fine matter were analyzed by hierarchical cluster analysis to determine the principal component of the two granulometric fractions. The main chemical difference between the two fractions was the greater abundance of carbonaceous particles in the fine fraction. We compared the ability of coarse and fine fractions, carbon black (CB), and residual oil fly ash (ROFA) to induce arachidonic acid release and tumor necrosis factor-alpha (TNF-alpha) production in the monocytic-macrophagic RAW 264.7 cell line at concentrations of 30 and 120 microg/mL. Our results showed that CB and ROFA were consistently less effective than both fractions of urban particles at inducing an inflammatory reaction in RAW 264.7 cells. Both PM fractions dose-dependently increased TNF-alpha production in RAW 264.7 cells after 5 and 24h of incubation, and only the TNF-alpha production induced by coarse particles at 30 microg/mL decreased significantly (P<0.01) after 24h of treatment. In our in vitro model the winter fine fraction was more reactive than the winter coarse fraction, in contrast to a previously examined summer sample. In the summer sample, coarse particles produced higher levels of inflammatory mediators than fine particles and the CB was consistently less effective than the urban particles. The different behaviors between summer and winter urban fractions may be due to their different physicochemical characteristics; in fact, the comparison of the two samples' characterization by SEM/EDX and X-ray photoelectron spectroscopy (XPS) analysis showed that in winter the carbonaceous particles are more abundant than in summer and that winter particles carry a greater quantity of organic compounds. We suggest that the higher concentration of organic compounds on fine carbonaceous particles may partially explain the higher activation of RAW 264.7 cells by fine particles.

Inflammatory mediators induced by coarse (PM2.5-10) and fine (PM2.5) urban air particles in RAW 264.7 cells.

Increased incidence of mortality and morbidity due to cardiopulmonary complications has been found to associate with elevated levels of urban air particles with an aerodynamic diameter <10 micron, PM10 and <2.5 micron, PM2.5. Respirable particles reach the lower respiratory tract where they are phagocytized by alveolar macrophages. Depending on particle composition, exposed macrophages may produce inflammatory mediators. A cascade impactor sampler was used to collect size-fractionated urban air particles. Particulate matter from the city of Rome (Italy) were collected onto stainless steel plates, and recovered using alcohol. The murine monocytic/macrophagic RAW 264.7 cell line was used to compare the ability of PM2.5-10, PM2.5 and carbon black to cause cell injury, such as arachidonic acid (AA) release, tumour necrosis factor alpha (TNF alpha) and interleukin (IL)-6 production. All test particles have been used at the same concentrations 30 and 120 microg/ml. Treatment with PM2.5-10 and PM2.5 induced significant AA release after 5 h of exposure at both concentrations, while carbon black was effective only at the higher concentration. After 5 h of incubation, PM2.5-10 and PM2.5 at 120 microg/ml induced 10 times the amount of TNF alpha than carbon black particles. The urban air particles-stimulated TNF alpha production decreased after 24 h of incubation while carbon black-stimulated TNF alpha was not. IL-6 production was induced by PM2.5 and by PM2.5-10 but not by carbon black. Carbon black was consistently less effective than the urban particles, suggesting that, the contaminants adsorbed on the particles are responsible for the release of inflammatory mediators.