Outer membrane (OM) protein F (porin) was purified by extraction from polyacrylamide gels of cell envelope proteins of the Pseudomonas aeruginosa PA01 strain. Mice were immunized intramuscularly with 10 micrograms of protein F preparation on days 1 and 14 and then subjected to burn and challenge on day 28. Protein F immunization afforded significant protection above that provided by PA01 lipopolysaccharide (LPS) immunization against subsequent challenge with six of six heterologous LPS immunotype strains of P. aeruginosa. By an ELISA, the murine immune response revealed an IgG titer of 5,120 to protein F by day 30. Immunoblot analysis of antisera from protein F-immunized mice revealed bands with both protein F and protein H of cell envelopes of all immunotypes tested. Active immunization with OM protein H did not, however, afford significant protection to mice in this burned mouse model. These data show the efficacy of OM protein F as a protective vaccine in a murine model representative of human infection.
OBJECTIVE -Diabetic patients have elevated blood levels of interleukin-6 (IL-6), which is known to increase inflammation and the development of vascular disease and atherosclerosis. This study examined the hypothesis that ketosis increases the circulating levels of IL-6 in type 1 diabetic patients as well as the secretion of IL-6 in vitro in a cell culture model using U937 monocytes.RESEARCH DESIGN AND METHODS -Fasting blood was obtained from type 1 diabetic patients and healthy siblings. To examine the effect of ketosis, U937 monocytes were cultured with ketone bodies (acetoacetate [AA], -hydroxybutyrate [BHB]) in the presence or absence of high glucose levels in the medium at 37°C for 24 h. IL-6 was determined by the sandwich enzyme-linked immunosorbent assay method, and intracellular reactive oxygen species (ROS) generation was detected using dihydroethidium dye. RESULTS-The blood level of IL-6 was higher in hyperketonemic (HK) diabetic patients than in normoketonemic (NK) diabetic patients (P Ͻ 0.05) and normal control subjects (P Ͻ 0.05). There was a significant correlation between ketosis and IL-6 levels (r ϭ 0.36, P Ͻ 0.04, n ϭ 34) in the blood of diabetic patients. Cell culture studies found that exogenous addition of the ketone body AA, but not BHB, increases IL-6 secretion and ROS generation in U937 cells. N-acetylcysteine (NAC) prevented the IL-6 secretion in acetoacetate-treated U937 monocytes.CONCLUSIONS -This study demonstrates that hyperketonemia increases IL-6 levels in the blood of type 1 diabetic patients and that NAC can inhibit IL-6 secretion by U937 monocytic cells cultured in a ketotic medium. Diabetes Care 26:2139 -2143, 2003I nterleukin-6 (IL-6), which is secreted by macrophages, lymphocytes, and other cells (1), is an important cytokine that can initiate events leading to atherogenesis by induction of adhesion molecules, monocyte-endothelial interactions, and inflammation injury (1-5). Anti-IL-6 therapy significantly prevents the inflammatory process in mice (6). The role of IL-6 in vascular inflammation has also been shown using IL-6 knockout mice that exhibit resistance to splanchnic artery occlusion shock (6), and in studies (7) that show increased levels of lipid peroxidation and inflammation in mice that overexpress IL-6. This suggests that elevated blood levels of IL-6 are associated with the development of vascular inflammation and atherosclerosis (1,2).IL-6 levels in blood are higher or similar in diabetic patients compared with normal subjects (4,8 -10). Cell culture studies have shown that high glucose concentrations can increase the IL-6 secretion in cultured monocytes (4,11,12). In addition to hyperglycemia, type 1 diabetic patients frequently experience ketosis (hyperketonemia) from excessive fat breakdown because body fuel is derived mainly from fat when the body is in a state of insulin deficiency (13). The blood concentration of ketone bodies (acetoacetate [AA], -hydroxybutyrate [BHB]) may reach 10 mmol/l in patients with severe ketosis, as compared with levels of Ͻ0.5 ...
A better understanding of how human immunodeficiency virus (HIV) coinfection affects the course of hepatitis C virus (HCV) infection is required to select patients with HIV who would benefit from current HCV therapy. Between June 1996 and March 2000, HCV RNA levels were quantified for 1,279 patients at the Louisiana State University Health Sciences Center; 28 of these patients were coinfected with HIV. HCV loads were quantified by the Bayer branched-DNA assay with a lower limit of detection of 0.2 Meq/ml. We compared the median HCV RNA levels of for patients coinfected with HIV and HCV and patients infected only with HCV who were in the same age range (23 to 55 years). The median HCV load for the 28 patients coinfected with HCV and HIV (17.8 Meq/ml) was significantly greater (P < 0.05) than that for similarly aged patients infected only with HCV (6.1 Meq/ml). The HCV load did not correlate with age or sex for either group of patients. A significant (R ؍ ؊0.4; P < 0.05) negative correlation was observed between HCV load and CD4 count in the coinfected group, for whom the CD4 counts at the time of HCV load analysis ranged from 6 to 1,773/mm 3 . The increased HCV load in patients coinfected with HCV and HIV compared to that in patients infected only with HCV and the inverse relationship of the HCV load to the CD4 count indicate that immunosuppression results in decreased control of HCV replication. In addition, we report significantly higher HCV loads among coinfected African Americans than Caucasians.
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