Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses.

Psoriasis vulgaris, a type-1 cytokine-mediated chronic skin disease, can be treated successfully with fumaric acid esters (FAE). Beneficial effects of this medication coincided with decreased production of IFN-gamma. Since dendritic cells (DC) regulate the differentiation of T helper (Th) cells, this study focussed on effects of monomethylfumarate (MMF, bioactive metabolite of FAE) on polarization of monocyte-derived DC.

Salmonella enterica serovar Typhimurium RamA, intracellular oxidative stress response, and bacterial virulence.

Escherichia coli and Salmonella enterica serovar Typhimurium have evolved genetic systems, such as the soxR/S and marA regulons, to detoxify reactive oxygen species, like superoxide, which are formed as by-products of metabolism. Superoxide also serves as a microbicidal effector mechanism of the host's phagocytes. Here, we investigate whether regulatory genes other than soxR/S and marA are active in response to oxidative stress in Salmonella and may function as virulence determinants.

The efficacy and safety of topical polymyxin B, neomycin and gramicidin for treatment of presumed bacterial corneal ulceration.

Aim: To evaluate the clinical efficacy and safety of topical polymyxin B, neomycin, and gramicidin for the treatment of suspected bacterial corneal ulceration at the Leiden University Medical Center.

Methods: Patients with a diagnosis of a suspected bacterial corneal ulcer between April 1995 and February 2002 were retrospectively identified and reviewed; clinical and microbiological features and response to therapy were analysed. All patients were treated with Polyspectran eye drops.

Plasma secretory leukocyte protease inhibitor in febrile patients.

Objectives: Secretory leukocyte protease inhibitor (SLPI) forms an integral part of the lung's defence, by its antimicrobial activity and by its ability to neutralize serine proteases that are released by granulocytes into the inflammatory exudate. Here, we investigate in febrile patients admitted to hospital whether plasma SLPI can serve as a marker of lung infection.

Methods: We prospectively determined the SLPI concentration in 152 febrile patients (median 73 [inter-quantile range (IQR): 58-82] year; 50% male) admitted to hospital because of infection of the airways (n = 44) or pneumonia (n = 108; i.

Human deficiencies in type-1 cytokine receptors reveal the essential role of type-1 cytokines in immunity to intracellular bacteria.

Human genetic factors play an important role in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae (reviewed in 1). The genetic elements involved and the mechanisms by which these control disease-susceptibility versus resistance, however, remain incompletely characterized. Recent studies on patients with idiopathic, severe infections due to poorly pathogenic mycobacteria and salmonellae have revealed that many of these patients are unable to produce or respond to IFN-gamma.

['Severe acute respiratory syndrome' (SARS): epidemiology, clinical signs, diagnosis and prevention].

Severe acute respiratory syndrome (SARS) is caused by a recently identified Coronavirus (SARS-CoV). The clinical symptoms are non-specific and during the first few days in particular, are not clinically distinguishable from those of many other viral or bacterial infections. The majority of infected patients develop pneumonia within a week of the first symptoms appearing.

TNF-alpha blockade and tuberculosis: better look before you leap.

According to several reports, the risk of active tuberculosis in patients who are latently infected with Mycobacterium tuberculosis is increased after treatment with tumour necrosis factor alpha (TNF)-blocking agents. These drugs have demonstrated effectiveness and are increasingly being used for treatment of several inflammatory diseases, including rheumatoid arthritis and Crohn's disease. Specialists prescribing TNF-blocking agents should be aware of the risk of tuberculosis and other infections, the unusual and severe clinical presentations and the available preventive measures.

Cytokine response to endotoxin in individuals heterozygous for the Delta32 mutation of chemokine receptor CCR5.

Studies of mice with a targeted disruption of the CCR5 gene suggest that the CC chemokine receptor 5 (CCR5) is a determinant of the cytokine response to endotoxin. In humans, a naturally occurring mutation of the CCR5 gene is a 32-basepair (bp) deletion which precludes the translation of the gene into a functional transmembrane protein. To evaluate the cytokine phenotype of heterozygosity for the 32 deletion, we studied the endotoxin-stimulated release of tumor necrosis factor-alpha, Interleukin (IL)-6, IL-8, IL-10, and IL-12 in whole blood ex-vivo of healthy volunteers and patients undergoing elective cardiac bypass surgery.

Responses to reactive oxygen intermediates and virulence of Salmonella typhimurium.

Salmonella typhimurium is an intracellular pathogen that can survive and replicate in macrophages. One of the host defense mechanisms that S. typhimurium encounters upon infection is superoxide produced by the phagocytes' NADPH-oxidase.

Genetic variations in the interleukin-12/interleukin-23 receptor (beta1) chain, and implications for IL-12 and IL-23 receptor structure and function.

Cell-mediated immunity (CMI) plays an essential role in human host defense against intracellular bacteria. Type-1 cytokines, particularly gamma interferon (IFN-gamma), interleukin-12 (IL-12), and IL-23, the major cytokines that regulate IFN-gamma production, are essential in CMI. This is illustrated by patients with unusual severe infections caused by poorly pathogenic mycobacteria and Salmonella species, in whom genetic deficiencies have been identified in several key genes in the type-1 cytokine pathway, including IL12RB1, the gene encoding the beta1 chain of the IL-12 and IL-23 receptors.

Beneficial effects of fumarate therapy in psoriasis vulgaris patients coincide with downregulation of type 1 cytokines.

Background: Fumarates have been shown to be effective in psoriasis vulgaris.

Objectives: To find out whether successful therapy is associated with modulation of cytokines.

Methods: We determined interferon (IFN)-gamma, interleukin (IL)-4 and IL-10 secretion capacities of peripheral blood mononuclear cells (PBMC) after phytohaemagglutinin stimulation, and IL-12p70 and IL-10 secretion capacities of PBMC after endotoxin stimulation in psoriasis vulgaris patients during treatment with fumarates.

Severe Mycobacterium bovis BCG infections in a large series of novel IL-12 receptor beta1 deficient patients and evidence for the existence of partial IL-12 receptor beta1 deficiency.

Cell mediated immunity plays a critical role in human host defence against intracellular bacteria. In patients with unusual, severe infections caused by poorly pathogenic species of mycobacteria and salmonellae, genetic deficiencies have been identified in key genes in the type-1 cytokine pathway, especially in IFNGR1 and IL12RB1. Here, we analyzed 11 patients originating from Turkey and suffering from unusual Mycobacterium bovis Bacille Calmette-Guerin infections following vaccination, and found that most patients (n=8) are deficient in IL-12Rbeta1 expression and function.

Synergistic activity of the N-terminal peptide of human lactoferrin and fluconazole against Candida species.

In light of the need for new antifungal regimens, we report that at noncandidacidal concentrations, the lactoferrin-derived peptide hLF(1-11), which is highly active against fluconazole-resistant Candida albicans, acts synergistically with fluconazole against this yeast and a fluconazole-sensitive C. albicans strain as well as C. glabrata, C.

Amputation-sparing treatment by nature: "surgical" maggots revisited.

Maggots were used as adjunct treatment for infected wounds that showed no response to the classical approach of wound debridement and antibiotic therapy. We summarize findings for 11 patients with necrotic wounds who received treatment with "surgical" maggots (100-2900 applied in 3-10 changes of dressing) for 11-34 days, which apparently aided in tissue remodeling and cure, and describe 2 typical patients in detail.

Tuberculin skin testing and in vitro T cell responses to ESAT-6 and culture filtrate protein 10 after infection with Mycobacterium marinum or M. kansasii.

T cell responses to ESAT-6 and culture filtrate protein 10 (CFP-10), antigens expressed by Mycobacterium tuberculosis but not by M. bovis bacille Calmette-Guérin (BCG), were found to discriminate reliably between infection with M. tuberculosis and BCG vaccination.

Periodontal infection in cancer patients treated with high-dose chemotherapy.

The infected and inflamed periodontium can act as a focus for systemic infection in neutropenic cancer patients. The incidence of these oral infections is unknown, but probably underestimated. Periodontal infections can easily be overlooked, primarily because symptoms of gingival inflammation may be minimal and the infection may be located in deeper parts of the periodontium.

Divergent role for TNF-alpha in IFN-gamma-induced killing of Toxoplasma gondii and Salmonella typhimurium contributes to selective susceptibility of patients with partial IFN-gamma receptor 1 deficiency.

Patients with defects in IFN-gamma- or IL-12-mediated immunity are susceptible to infections with Salmonella and non-tuberculous mycobacteria, but rarely suffer from infections with other intracellular pathogens such as Toxoplasma gondii. Here we describe macrophage and T cell function in eight individuals with partial IFN-gamma receptor 1 (IFN-gammaR1) deficiency due to a mutation that results in elevated cell surface expression of a truncated IFN-gammaR1 receptor that lacks the intracellular domain. We show that various effector mechanisms dependent on IFN-gammaR signaling are affected to different extents.

Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae.

Host genetic factors are important in determining the outcome of infections caused by intracellular pathogens, including mycobacteria and salmonellae, but until now have been poorly characterized. Recently, some individuals with severe infections due to otherwise weakly pathogenic mycobacteria (non-tuberculous mycobacteria or Mycobacterium bovis bacille Calmette-Guérin) or Salmonella species have been shown to be unable to produce or respond to interferon-gamma. This inability results from mutations in any of five genes encoding essential proteins of the type 1 cytokine cascade: interleukin-12p40, interleukin-12R beta 1, interferon-gamma R1, interferon-gamma R2 or STAT1.

Recurrent staphylococcal bacteraemia and subhepatic abscess associated with gallstones spilled during laparoscopic cholecystectomy two years earlier.

This is the first report of Staphylococcus aureus bacteraemia and subhepatic abscess in association with intraperitoneal gallstones spilled during laparoscopic cholecystectomy two years earlier. Spilled gallstones can lead to abscess formation in the late postoperative period by acting as foreign bodies that can become infected during bacteraemia and then become a source of recurrent bacteraemia.

Bacterial infections of the orbit.

This review of the literature on orbital infections focusses on bacterial infections of the preseptal space, subperiosteal abscesses, orbital phlegmon and orbital abscesses. The need for a timely diagnosis of and multidisciplinary approach to treatment of these infections, which may lead to life-threatening complications, is emphasized.