Several genes coding for different cytokines may affect host susceptibility to tuberculosis. This study investigates the relationship of the single base change polymorphic variants identified in the first intron of interferon-gamma (+874 T/A) and in the promoter region of interleukin-10 gene (-1,082 G/A), with cytokine production by peripheral blood mononuclear cells and tuberculosis susceptibility. We studied a Spanish population of 113 patients with culture-proven pulmonary tuberculosis, 207 healthy close contacts (125 tuberculin reactive and 82 tuberculin negative), and 100 healthy tuberculin-negative control subjects. Multiple logistic regression analysis showed that individuals homozygous for the interferon-gamma (+874) A allele had a 3.75-fold increased risk of developing tuberculosis (95% confidence interval, 2.26-6.23, p = 0.0017). Stimulated production of interferon-gamma by peripheral mononuclear cells from patients with genotype AA was depressed compared with that of non-AA homozygotes at the time of diagnosis and after completion of therapy. Multivariate analysis showed that the presence of an AA genotype and the absolute number of lymphocytes were the only independent predictors of interferon-gamma production. In contrast, the different rates of interleukin-10 production associated with the interleukin-10 polymorphism did not affect susceptibility to tuberculosis. Thus, a genetic defect in the production of interferon-gamma in individuals homozygous for the (+874) A allele could contribute to their increased risk of developing tuberculosis.

The relationship between fluctuating cytokine concentrations in plasma and the outcome of sepsis is complex. We postulated that early measurement of the activation of nuclear factor B (NF-B), a transcriptional regulatory protein involved in proinflammatory cytokine expression, may help to predict the outcome of sepsis. We determined NF-B activation in peripheral blood mononuclear cells of 34 patients with severe sepsis (23 survivors and 11 nonsurvivors) and serial concentrations of inflammatory cytokines (interleukin-6, interleukin-1, and tumor necrosis factor) and various endogenous antagonists in plasma. NF-B activity was significantly higher in nonsurvivors and correlated strongly with the severity of illness (APACHE II score), although neither was related to the cytokine levels. Apart from NF-B activity, the interleukin-1 receptor antagonist was the only cytokine tested whose level in plasma was of value in predicting mortality by logistic regression analysis. These results underscore the prognostic value of early measurement of NF-B activity in patients with severe sepsis.Many reports have focused on aspects of the proinflammatory cytokine network, which is believed to be central to the pathophysiology of the sepsis syndrome (5,8). However, the cytokine responses in patients with sepsis appears to vary so much between individuals (10) that the prognostic usefulness of circulating cytokine concentrations is often less than that of clinical variables, such as the acute physiology and chronic health evaluation (APACHE) II or III (9). Other studies indicate that the problem in overwhelming sepsis is not that inflammatory cytokines are expressed but, rather, that their expression is not properly modulated by anti-inflammatory mediators (16,17). Recent investigations by others (3) and ourselves (1) searching for new clinically reliable markers in patients with sepsis have shown that circulating leptin levels, whose secretion is closely linked to the activation of the cytokine cascade (1), may help to predict mortality in sepsis and septic shock.Among several transcriptional regulatory factors involved in immunoregulatory genes expression, nuclear factor kappa B (NF-B) acts at a critical step for directing the transcription of many proinflammatory genes in animal models of inflammatory diseases (6, 7). Investigations regarding the role of NF-B in human inflammatory diseases are scarce (2, 15). So far, no study has aimed to examine in patients with sepsis the relationship between the concentrations of some components of the proinflammatory and anti-inflammatory cytokine response in plasma, NF-B expression in peripheral blood mononuclear cells, and clinical outcome. We hypothesized that severe, fatal sepsis could be distinguished from less severe sepsis by demonstrating greater NF-B activation and decreased anti-inflammatory response. Thus, this study compared the prognostic value of combining measurements of NF-B activity in circulating blood cells and the cytokine profile in plasma in patients with severe sepsis. ...

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Fifty-four cases of Achromobacter xylosoxidans bacteremia diagnosed over a 10-year period in patients from 2 months to 87 years of age were reviewed. Fifty-two episodes were nosocomial. The most frequent underlying condition was neoplasm (solid or hematological). The source of infection was a contaminated intravenous catheter in 35 patients (60%) and pneumonia in 6 patients. Eight (15%) patients died. The only risk factors significantly associated with mortality were age over 65 years and neutropenia. The results of in vitro susceptibility studies of the isolates showed that antibiotic therapy with antipseudomonal penicillins or carbapenems would be a reasonable choice. An epidemiological study conducted in the hemodialysis unit showed Achromobacter xylosoxidans in tap water and on the hands of two healthcare workers but not in the hemodialysis systems. Patients were probably contaminated when healthcare workers manipulated the intravenous catheters without wearing gloves.

SUMMARY Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur.