concanavalin-a and Pneumonia

immunodepression after stroke is associated with complications like high infection rate, but its role in aneurysmal subarachnoid hemorrhage (aSAH) is unclear. This pilot study aimed to assess the presence of immunodepression and its association with infections after aSAH.. sixteen aSAH patients were enrolled in a prospective study on immune function in a single institution. Detailed immune monitoring (peripheral blood leukocyte subsets, monocyte human leukocyte antigen-DR expression, ex vivo lipopolysaccharide-induced monocytic, Concanavalin A-induced lymphocytic cytokine secretion) was performed until day 10 after aSAH. Occurrence of infection was assessed within 14 days after aSAH.. sixteen consecutive aSAH patients (53.1 ± 10.2 years; mean ± SD) met the inclusion criteria, classified as asymptomatic (World Federation of Neurological Surgeons; median, 1; quartile, 1-1; n=7) and symptomatic (median, 4; quartile, 3-5; n=9), all presenting with acute neurological deficits, and 5 of these had additional delayed cerebral ischemia. T-lymphopenia, impaired ex vivo lymphocytic/monocytic cytokine secretion, and decreased monocyte human leukocyte antigen-DR expression occurred over all World Federation of Neurological Surgeons grades but persisted beyond day 3 only in symptomatic patients. Pneumonia (67%; P=0.011) was more frequent in symptomatic patients. Already at day 1, patients with pneumonia showed significantly lower T-cell counts and mitogen-induced interferon-γ production compared to patients without infections.. a pronounced SAH-induced immunodepression was observed early after aSAH but persisted only in symptomatic patients. Immunodepression was associated with a high incidence of pneumonia. Early diagnosis of immunodepression might allow targeted treatment to prevent infectious complications after aSAH.

Topics: Adult; Cells, Cultured; Concanavalin A; Female; Gene Expression Regulation; HLA-DR Antigens; Humans; Immune Tolerance; Infections; Interferon-gamma; Lipopolysaccharides; Lymphocytes; Male; Middle Aged; Mitogens; Monocytes; Pneumonia; Prospective Studies; Subarachnoid Hemorrhage; Time Factors

Dietary fat intake has been associated with obesity and obesity in its turn with attenuated airway function and asthma, but it is unclear whether or how high-fat intake per se alters immune function relevant to development of allergic asthma.. To use a non-obese mouse model of mild to moderate allergic asthma to compare effects of high-fat with isocaloric control-diet on allergic immune responses.. C57BL/6 mice weaned and maintained on control (11% fat calories) or isocaloric high-fat diet (58% fat calories) were systemically sensitized with ovalbumin and challenged in the lungs. Allergic airway inflammation was assessed by measuring lung inflammation; serum antibodies; and, cytokines in serum, bronchoalveolar lavage (BAL) fluid and in supernatants of in vitro stimulated lung draining lymph node and spleen lymphocytes.. There was a significant reduction in lung eosinophilia and IL-5 in high-fat fed mice. Lung draining lymph node cells from these mice showed reduced pro-inflammatory cytokine (MCP-1 and TNF-alpha) release after ovalbumin re-stimulation and reduced release of IL-13 after concanavalin-A stimulation, indicating a general rather than just an antigen-specific change. There was no difference in IFN-gamma release. In contrast, pro-inflammatory cytokine release was increased from splenocytes. Decreased eosinophilia was not due to increased regulatory T cell or IL-10 induction in draining lymph nodes or spleen, nor to changes in antibody response to ovalbumin. However, decreased levels of serum and BAL eotaxin were found in high-fat fed animals.. The data indicate that high-fat dietary content redirects local immune responses to allergen in the lungs and systemic responses in the spleen and serum. These effects are not due to changes in regulatory T cell populations but may reflect a failure to mobilize eosinophils in response to allergic challenge.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cells, Cultured; Concanavalin A; Cytokines; Dietary Fats; Disease Models, Animal; Lung; Lymph Nodes; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Ovalbumin; Pneumonia; Pulmonary Eosinophilia; T-Lymphocytes, Regulatory

p59fynT is a protein tyrosine kinase in the src family that has been associated with and believed to function in the signaling of many receptors, including the T-cell receptor. A role for the kinase in antigen-driven pulmonary inflammation was examined using mice whose p59fynT gene had been genetically ablated. FynKO mice that were sensitized to ovalbumin exhibited a marked increase in bronchoalveolar lavage eosinophils and cytokines, including interleukin (IL)-4 and IL-5, relative to wild-type mice in response to antigen aerosol exposure. Ovalbumin-stimulated IL-5 production was also increased in cultured splenocytes derived from fynKO mice relative to wild-type mice, whereas interferon-gamma levels were unchanged. Diminished concanavalin A--stimulated IL-4 levels from fynKO splenocytes were consistent with reduced serum immunoglobulin (Ig)E levels observed in sensitized/saline aerosol-challenged animals and may reflect defective natural killer 1.1(+) T cell development. Normalization of IgE levels in sensitized fynKO mice relative to wild-type mice occurred after repeat antigen challenge, which suggests a secondary source of IL-4. Overall, these data demonstrate fyn is a negative regulator of allergic airway inflammation in mice because its absence promotes a shift to a T helper-2 phenotype that may reflect the kinase's role in T-cell receptor signaling.

Topics: Animals; Antigens; Bronchoalveolar Lavage Fluid; Concanavalin A; Disease Models, Animal; Eosinophils; Hypersensitivity; Immunoglobulin E; Interleukin-4; Interleukin-5; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Pneumonia; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fyn; Spleen; src-Family Kinases; Th2 Cells

The hyporesponsive state of lung-derived mononuclear leukocytes has been, in part, attributed to the effects of the lipid rather than the protein components of pulmonary surfactant. In the present study, however, the results suggest that purified preparations of pulmonary surfactant-associated protein A (SP-A) suppress both phytohemagglutinin (PHA, 1 microgram/ml)- and anti-CD-3 (1 to 10 ng/ml) activated proliferation of human peripheral blood and tonsillar mononuclear cells in a dose-dependent manner at concentrations as low as 50 pM (6.25 micrograms/ml) when added at the initiation of cultures. Addition of SP-A to PHA-stimulated peripheral blood mononuclear cells (PBMC) as late as 24 to 36 h after PHA was also capable of suppressing [3H]thymidine incorporation measured at 72 h. In contrast, concanavalin A (Con A; 2 micrograms/ml)-stimulated PBMC proliferation was slightly augmented by the addition of SP-A. Analysis of the supernatants of PHA-stimulated cultures treated with SP-A revealed that accompanying the inhibition of proliferation was a corresponding decline in measurable interleukin-2 (IL-2) concentrations, from 154 pg/ml for the PHA-treated cells to 57.8, 28.4, 5.2, and less than 2 pg/ml of IL-2 when SP-A was added at 6.25, 12.5, 25, and 50 micrograms/ml, respectively. We suggest that the action of SP-A on PHA-stimulated human PBMC may involve the blocking of a costimulatory signal crucial for in vitro T-cell activation.

Topics: Animals; Antibodies, Monoclonal; Cattle; CD3 Complex; Cell Division; Cell Line; Concanavalin A; Glycoproteins; Humans; Interleukin-2; Lymphocyte Activation; Monocytes; Pneumonia; Proteolipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Proteins; Pulmonary Surfactants; Recombinant Proteins; T-Lymphocytes

Pretreatment of the lung graft with concanavalin A (Con A) or chondroitin sulfate (CIS) was used to modify the lung allograft response after transplantation into moderately immunosuppressed (low doses of azathioprine and prednisone) recipients. Significant (p less than 0.05) prolongation of survival was observed after graft pretreatment. Pneumonia and rejection were the most frequent causes of death for all groups of dogs. However, only 3 out of 6 animals from each of the groups with pretreated grafts died of pneumonia or rejection, whereas 5 of the 6 animals in the control group died of these causes. Furthermore, when rejection occurred in the dogs with lung grafts pretreated with Con A or CIS, it was considerably delayed compared with the controls. Partial pressure of arterial oxygen, chest roentgenograms, and lung histology were good indicators of lung viability after transplantation.

Topics: Animals; Chondroitin; Chondroitin Sulfates; Concanavalin A; Dogs; Female; Graft Rejection; Lung; Lung Transplantation; Male; Pneumonia; Postoperative Complications; Radiography; Transplantation, Homologous