ABSTRACT
As part of the innate immune system, Toll-like receptors (TLRs) react rapidly on a pathogen challenge without prior exposure. Although it is well known that TLR4 is associated with the receptor for lipopolysaccharide (LPS), its role during sepsis has not yet been clearly defined. To study this,polymicrobial sepsis was induced in male C3H/HeN (TLR4 wild type) and C3H/HeJ (TLR4 mutant) mice by caecal ligation and puncture (CLP).A total of 48 h following the surgical procedure, the mice were sacrificed and plasma was collected.Kupffer cells were isolated and ex vivo cytokine production and plasma levels were determined. Lung neutrophil influx was investigated by myeloperoxidase (MPO) content and immunohistochemistry. T-cell subtypes in blood and spleen were determined by flow cytometry.Mice with intact TLR4 (wild type) had increased Kupffer cell IL-6 production and increased plasma levels as compared with C3H/HeJ mice following sepsis. Furthermore, wild type mice showed increased neutrophil influx in lungs and lower percentages of CD8+ splenocytes. This was accompanied with less activity, increased weight loss and decreased core temperature.We conclude that TLR4 influences the humoral and cellular response during the course of sepsis and lack of TLR4 reduces markers of the systemic inflammatory response as well as distant organ damage.Therefore, TLR4 could act as a future therapeutic target modulating the immune response during sepsis.
Subject(s)
Humeral Fractures/immunology , Immunity, Cellular/immunology , Interleukin-6/blood , Kupffer Cells/immunology , Sepsis/immunology , Toll-Like Receptor 4/immunology , Animals , Interleukin-6/immunology , Kupffer Cells/metabolism , Male , Mice , Mice, Inbred C3H , Mutation , Sepsis/blood , Toll-Like Receptor 4/blood , Toll-Like Receptor 4/geneticsABSTRACT
We studied tissue samples of noninfected delayed union or nonunion of diaphyseal bones in 10 patients immunopathologically and neuroimmunologically 4 to 25 months after the primary injury. Samples mostly consisted of vascularized connective tissue of varying density with the proline-4-hydroxylase-containing fibroblast as the major cell type. Most inflammatory cells were CD4 T-lymphocytes and their number was always twice that of the CD8 positive cells. Staining for CD11b positive monocyte/macrophages showed in all samples positive cells scattered in the connective tissue stroma with perivascular enrichments. Mast cells were absent or very rare. Our findings suggest that delayed union and nonunion tissue consists of vascularized connective tissue, which mostly contains 5B5 fibroblasts, CD11b macrophages and vascular endothelial cells with only few immigrant recently recruited monocytes or lymphoid cells. Almost all resident cells seem to be involved in tissue remodeling as suggested by their content of fibroblast-type MMP-1 and its proteolytic activator MMP-3 or stromelysin. The most striking finding was the paucity or total lack of peripheral innervation, which may have to do with the nonunion of the fracture.
Subject(s)
CD4-CD8 Ratio , Fractures, Ununited/immunology , Humeral Fractures/immunology , Tibial Fractures/immunology , Adolescent , Adult , Antigens, CD/analysis , Endothelium, Vascular/pathology , Female , Fibroblasts/pathology , Fractures, Ununited/pathology , Humans , Humeral Fractures/pathology , Immunoenzyme Techniques , Macrophages/pathology , Male , Middle Aged , Peripheral Nerves/chemistry , Tibial Fractures/pathologyABSTRACT
The level of immunoglobulins, complement and properdin, data of leukograms were studied in 40 patients with closed fractures of bones with noncomplicated and complicated (by a purulent infection) course of the posttraumatic period. The authors have established variants of changes of these parameters, their correlation with the adaptation reactions of the organism and severity of the trauma.
