ovalbumin and Sepsis

During sepsis, CD4 T cells express activation markers within the first 24 h. In the present study, the mechanisms of T-cell activation and its consequences were addressed in an acute peritonitis model in mice. The response of CD4+ T cells to sepsis induction was compared between OTII mice, characterized by ovalbumin-specific T-cell receptor-transgenic T cells, and C57BL/6 controls (wild type [WT] mice). Because ovalbumin was absent during peritonitis, the OTII CD4+ T cells could not be activated by canonical antigen recognition. In both OTII and WT control mice, CD4+ T effector cells and CD4+ Foxp3+ regulatory T cells (Tregs) expressed the activation marker CD69 early after sepsis onset. However, full activation with upregulation of CD25 and proliferation took place only in the presence of the antigen. Besides this, the fraction of Tregs was lower in OTII than that in WT mice. Sepsis mortality was increased in OTII mice. Our data show that, in sepsis, partial activation of CD4+ T cells is induced by a T-cell receptor-independent pathway, whereas full stimulation and proliferation require a specific antigen. Antigen-dependent T-cell effector functions as well as Treg activity may contribute to sepsis survival.

Topics: Acute Disease; Adoptive Transfer; Animals; CD4-Positive T-Lymphocytes; Cell Proliferation; Disease Models, Animal; Female; Lymphocyte Activation; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin; Peritonitis; Sepsis; T-Cell Antigen Receptor Specificity; T-Lymphocytes, Regulatory

The effects of small-molecule p38 inhibitors in numerous models of different disease states have been published, including those of SD-282, an indole-5-carboxamide inhibitor. The aim of the present study was to evaluate the pharmacological activity of SD-282 on cytokine production in vitro as well as in 2 in vivo models of inflammation in order to illuminate the role of this particular inhibitor in diverse disease states. The results presented here provide further characterization of SD-282 and provide a context in which to interpret the activity of this p38 inhibitor in models of arthritis, pain, myocardial injury, sepsis and asthma; all of which have an inflammatory component. SD-282 represents a valuable tool to elucidate the role of p38 MAP kinase in multiple models of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Disease Models, Animal; Enzyme Inhibitors; Female; Granulocytes; Guinea Pigs; Humans; In Vitro Techniques; Indoles; Inflammation; Lung; Male; Mice; Mice, Inbred BALB C; Ovalbumin; p38 Mitogen-Activated Protein Kinases; Sepsis; Tumor Necrosis Factor-alpha

Topics: Abdomen; Animals; Biomarkers; Edetic Acid; In Vitro Techniques; Intestinal Mucosa; Male; Ovalbumin; Permeability; Rats; Rats, Sprague-Dawley; Sepsis

The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats.. The different-sized intestinal absorption markers 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51Cr-EDTA.. In comparison with the sham-operated rats, septic rats had higher 51Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption.. The results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit.

Topics: Animals; Bacteroides fragilis; Bacteroides Infections; Chromium Radioisotopes; Edetic Acid; Escherichia coli Infections; Gastrointestinal Transit; Intestinal Absorption; Male; Ovalbumin; Rats; Rats, Sprague-Dawley; Sepsis; Time Factors

Topics: Abscess; Candida; Hypersensitivity; Kidney Diseases; Liver Abscess; Lung Abscess; Ovalbumin; Pathology; Rats; Research; Sepsis; Staphylococcal Infections