Induction of Experimental Chronic Arthritis in Rabbits by Cell-free Fragments of Erysipelothrix

A cell-free crude extract of Erysipelothrix rhusiopathiae injected by high pressure jet into the knee-joint of rabbits stimulated an acute, mild inflammatory reaction. Additional injections at 3-day intervals induced a chronic condition characterized by hyperplasia of the synovial cells and hypertrophy of the villi, due to infiltration by lymphocytes and plasma cells which formed aggregates resembling Allison-Ghormley bodies. There was also extensive proliferation of stroma vasculature and fibrous tissue. A similar jet injection of the diluent produced an early, transient, acute, and mild inflammation. A mechanism is postulated for fixation of one or more of the chemically characterized antigens in or near the synovium as a means of inducing the localized inflammatory response that predisposes the joint to infection.     

Synergistic cytotoxicity. I. Characterization of a heat labile plasma fraction that induces nonspecific cytotoxicity by human mononuclear cells.

The mechanism by which non-immune mononuclear cells recognize invading foreign material and are activated for cytotoxic attack was studied in a model system employing human mononuclear cells, fresh plasma, and 51Cr-labeled xenogeneic target erythrocytes. In these experiments, fresh antibody-depleted plasma or mononuclear leukocytes alone were poorly cytotoxic to xenogenic erythrocytes. However, these target cells were rapidly lysed when both fresh antibody-depleted plasma and mononuclear cells were present in the assay. The plasma factor could not be removed by extensive absorption with the target cells, was present in plasma from hypogammaglobulinemic patients, was heat labile, and was sensitive to incubation with zymosan and cobra venom factor. The "antigen" specificity of this reaction was directed by the serum factor inasmuch as target cells autologous to the effector cells could be killed in the presence of antibody-depleted xenogeneic plasma, but not autologous plasma. These data suggest that an important mechanism for the recognition of "foreigness" by non-immune mononuclear cells is via interaction with a plasma component, possibly a factor related to serum complement.     

CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response

Infarct healing is dependent on an inflammatory reaction that results in leukocyte infiltration and clearance of the wound from dead cells and matrix debris. However, optimal infarct healing requires timely activation of "stop signals" that suppress inflammatory mediator synthesis and mediate resolution of the inflammatory infiltrate, promoting formation of a scar. A growing body of evidence suggests that interactions involving the transmembrane receptor CD44 may play an important role in resolution of inflammation and migration of fibroblasts in injured tissues. We examined the role of CD44 signaling in infarct healing and cardiac remodeling using a mouse model of reperfused infarction. CD44 expression was markedly induced in the infarcted myocardium and was localized on infiltrating leukocytes, wound myofibroblasts, and vascular cells. In comparison with wild-type mice, CD44(-/-) animals showed enhanced and prolonged neutrophil and macrophage infiltration and increased expression of proinflammatory cytokines following myocardial infarction. In CD44(null) infarcts, the enhanced inflammatory phase was followed by decreased fibroblast infiltration, reduced collagen deposition, and diminished proliferative activity. Isolated CD44(null) cardiac fibroblasts had reduced proliferation upon stimulation with serum and decreased collagen synthesis in response to TGF-beta in comparison to wild-type fibroblasts. The healing defects in CD44(-/-) mice were associated with enhanced dilative remodeling of the infarcted ventricle, without affecting the size of the infarct. Our findings suggest that CD44-mediated interactions are critically involved in infarct healing. CD44 signaling is important for resolution of the postinfarction inflammatory reaction and regulates fibroblast function.     

Histopathological observations of spontaneous regression of Rous sarcomas in Japanese quails.

Turmors induced in Japanese quails by the Schmidt-Ruppin strain of Rous sarcoma virus were examined histopathologically. The following three phases were recognized in the quails whose tumors regressed finally (regressor). Phase I was between days 4 and 7 of virus inoculation, when growth of tumor cells was seen with predominant infiltration of heterophils. Phase II, from days 10 to 14, was characterized by necrosis of tumor cells and focal accumulation of lymphoid cells which frequently formed follicle-like nodules. In phase III from days 18 to 24, tumor cells and heterophils disappeared, whereas diffuse infilitration of lymphoid cells, plasma cells and histiocytes were demonstrated. In the quails whose tumors progressed (progressor), growth of tumor cells and infiltration of heterophils at phase I seemed to follow a pattern similar to that of regressors, but subsequent infiltration and focal accumulation of lymphoid cells were rare. These morphological findings suggested an immunological reaction against tumor cells by lymphoid cells.     

Antioxidant status (CoQ10 and Vit. E levels) and immunohistochemical analysis of soft tissues in periodontal diseases

Reactive oxygen species and antioxidant status in periodontal diseases and periodontal-related pathologies is an item of growing interest. Immunohistochemical approach may be usefully employed in the study of soft tissues affected by periodontal disease, giving valuable information on tissue morphology and vascular proliferation that depends directly on the inflammatory state. In order to study CoQ(10) and vitamin E content in healthy gingiva and in gingivitis a new adaptation to previously published methods for their determination was adopted. During gingivitis tissue displayed a large inflammatory infiltration in the lamina propria and a VEGF positive squamous epithelium. The inflammatory infiltration consisted mainly of lymphocytes, plasma cells and neutrophils. Vitamin E dramatically decreased and CoQ(10) remained unchanged despite the increased amount of cells present in the periodontally affected tissues, indicating that continuous oxidative stress which occurred in these structure affected the antioxidant pattern of the tissue.     

Pro-Inflammatory Action of MIF in Acute Myocardial Infarction via Activation of Peripheral Blood Mononuclear Cells

Objectives

Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI).

Methods and Results

We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in cultured peripheral blood mononuclear cells (PBMCs) and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1β which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI.

Conclusion

MI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests that MIF could be a potential therapeutic target following MI.     

Histopathology of Chlamydia trachomatis salpingitis after primary and repeated reinfections in the monkey subcutaneous pocket model

Monkeys with subcutaneously autotransplanted salpingeal fimbrial tissues were subjected to primary and repeated infections with Chlamydia trachomatis. The inflammatory response after primary inoculation was characterized by infiltration with polymorphonuclear leucocytes in the acute phase and mononuclear cells in the chronic phase. However, the inflammatory response after repeated infections was dominated by a mononuclear cell infiltration with a conspicuous absence of the initial phase of polymorphonuclear leucocyte infiltration. The remarkable findings of repeated infections were plasma cell infiltration, lymphoid follicle formation, and increased fibroblast activity resulting in extensive fibrosis. These findings are similar to those described for monkeys inoculated directly into the oviducts with C. trachomatis and support our original hypothesis that, after chlamydial infection, the tissue damage is provoked by immune-mediated mechanisms.     

Critical role for mast cells in the pathogenesis of 2,4-dinitrobenzene-induced murine colonic hypersensitivity reaction

The immunological mechanisms underlying the role of mast cells in the pathogenesis of inflammatory bowel disease (IBD) are poorly defined. In this study, non-IgE mediated colonic hypersensitivity responses in BALB/c mice induced by skin sensitization with dinitrofluorobenzene (DNFB) followed by an intrarectal challenge with dinitrobenzene sulfonic acid featured as a model to study the role of mast cells in the development of IBD. Vehicle- or DNFB-sensitized mice were monitored for clinical symptoms and inflammation 72 h after dinitrobenzene sulfonic acid challenge. DNFB-sensitized mice developed diarrheic stool, increased colonic vascular permeability, hypertrophy of colonic lymphoid follicles (colonic patches), and showed cellular infiltration at the microscopic level. Increased numbers of mast cells were found in the colon of DNFB-sensitized mice located in and around colonic patches associated with elevated levels of mouse mast cell protease-1 in plasma indicating mast cell activation. Colonic patches of DNFB mice, stimulated in vitro with stem cell factor indicated that an increase in TNF-alpha levels in the colon is mainly mast cell originated. Finally, neutrophil infiltration was observed in the colon of DNFB-sensitized mice. Induction of this model in mast cell-deficient WBB6F(1) W/W(v) mice shows a profound reduction of characteristics of the colonic hypersensitivity reaction. Reconstitution with bone marrow-derived mast cells in WBB6F(1) W/W(v) mice fully restored the inflammatory response. This study demonstrates the importance of mast cells in the development of clinical symptoms and inflammation in the presented murine model for IBD.     

Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry detecting NOS in healthy and chronically inflamed pulp

The aim of this study was to examine the expression of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity in human dental pulps and determine whether there are changes of the activity in chronically inflamed pulp tissue. Nineteen pulps with clinical diagnosis of chronic pulpitis were collected during endodontic treatment. The healthy controls were obtained from teeth extracted for orthodontic therapy. The clinical diagnosis was confirmed by histological analysis. Healthy pulps showed stratified odontoblasts in peripheral parts, while in central area there was normal connective tissue. Chronically inflamed pulps showed less expressed stratification of odontoblasts and infiltration of lymphocytes, polymorphonuclear leukocytes, plasma cells and mastocytes. NADPH-d granular reactivity was assessed semi quantitatively under the light microscope by a single observer and scored on an intensity scale from negative reaction to very strong reaction. In healthy human pulps, NADPH-d activity was strong to very strong in odontoblastic layer. Endothelial cells and Schwann cells showed strong NADPH-d reactivity, while the other parts of central area were weakly positive. Similar distribution of reactivity was expressed also in chronically inflamed pulp; moderate to strong reaction was observed in stromal area as result of positive reaction in inflammatory cells and endothelial cells of abundant newly formed capillaries.     

Effect of ultrasonically nebulized distilled water on airway epithelial cell swelling in guinea pigs.

To investigate the pathogenesis of ultrasonically nebulized distilled water-induced airway narrowing, we studied the role of airway epithelial cells during a distilled water-inhalation challenge in an animal model of airway inflammation. Guinea pigs were divided into four groups: 1) a sham/saline (S/S) group: sham ozone followed by saline inhalation; 2) a sham/water (S/W) group: sham ozone followed by water inhalation; 3) an ozone/saline (O/S) group: ozone followed by saline inhalation; and 4) an ozone/water (O/W) group: ozone followed by water inhalation. After exposure to either 3.0 parts/million ozone or air at the same flow rate for 2 h, guinea pigs were anesthetized and tracheostomized, and then lung resistance (RL) was measured. For morphometric assessment, tissues were fixed with formaldehyde, stained with hematoxylin and eosin, and cut into transverse sections. Airway dimensions were either measured directly or calculated from the internal perimeter, the external perimeter, and airway wall area. There were no statistical differences in the values of RL before distilled water inhalation between the sham groups and the ozone groups. RL increased significantly after 10 min of distilled water inhalation in both the S/W group and the O/W group. In the S/W group, epithelial cells were swollen, and intercellular spaces were wider, resulting in significant increase in epithelial wall thickness, but there was no significant infiltration by inflammatory cells. In the O/S group, the epithelium showed infiltration by inflammatory cells without change in cell volume. In the O/W group, the epithelium showed both infiltration and a greater increase in epithelial wall thickness compared with the S/W group. These results suggest that airway epithelial cell swelling, induced by inhaled distilled water, increases with RL in guinea pigs and that this reaction may be accelerated by airway inflammation.     

Eosinophil degranulation. An immunologic determinant in the pathogenesis of the Mazzotti reaction in human onchocerciasis

Onchocerciasis patients treated with diethylcarbamazine often undergo a severe inflammatory response, the Mazzotti reaction. To assess the eosinophil's role in the pathogenesis of the Mazzotti reaction, we obtained serial blood, plasma, and skin biopsy specimens from 21 heavily infected patients and 3 endemic controls, both before and during therapy with diethylcarbamazine. Samples were analyzed for blood eosinophils, plasma levels of eosinophil granule major basic protein (MBP) and eosinophil-derived neurotoxin, eosinophil infiltration and eosinophil and mast cell degranulation in the skin. After the first dose of diethylcarbamazine, blood eosinophils fell from a pre-treatment level of 888 +/- 111 to 203 +/- 42 cells/mm3 at 8 h. This decrease was followed by a marked eosinophilia developing over the remaining 7 days of treatment and 14 days of follow-up. Plasma eosinophil-derived neurotoxin levels increased from 56 +/- 4 ng/ml pretreatment to a peak of 82 +/- 9 ng/ml at 8 h and returned to pretreatment levels by 48 h. Beginning at 12 h, plasma MBP levels increased from 730 +/- 74 ng/ml pretreatment to a peak of 1140 +/- 74 ng/ml after 5 days. Pretreatment skin biopsies stained for MBP by immunofluorescence showed a bright fibrillar pattern in the dermis consistent with chronic eosinophil degranulation; the MBP was localized on elastic tissue fibers. After treatment, skin biopsy specimens showed both the pretreatment fibrillar MBP staining pattern as well as focal eosinophil degranulation. Deposition of MBP around microfilariae in the papillary dermis was visible as early as 1.5 h. The lowest blood eosinophil levels and peak plasma eosinophil-derived neurotoxin levels coincided with the infiltration and degranulation of eosinophils in the skin. Mast cell degranulation in the skin was maximal by the first posttreatment biopsy (1.5 h) coincident with the beginning of eosinophil degranulation. Although the pathogenesis of the Mazzotti reaction is clearly complex, our results indicate that eosinophil degranulation is characteristic of the response and that it occurs with a time course suggestive of a role for the eosinophil in determining the clinical and pathologic manifestations of the reaction.     

Vitamin B6-deficient diet plus 4-deoxypyridoxine (4-DPD) reduces the inflammatory response induced by T. spiralis in diaphragm,masseter and heart muscle tissue of mice

Animals fed diets deficient in vitamin B6 develop microcytic anemia, alterations of growth, and other pathologies. 4-deoxypirydoxine is a potent antagonist of vitamin B6 coenzyme which depresses IL-1, TNF and IL-6 and has anti-inflammatory properties. The aim of this study was to show the anti-infl ammatory effects of 4-DPD on chronic inflammation caused by the nematode parasite T. spiralis, specifically on the recruitment and the activation of inflammatory cells. Two groups of mice, 6 weeks of age, were used: one was maintained on a vitamin B6-deficient synthetic pellet diet for 15 days before injection of the nematode, and administered an intraperitoneal injection (i.p.) of 4-DPD (250 g/mouse) for 15 days (the first, 5 days before infection), and the second group was maintained on a normal diet for the total duration of the experiment. These two groups were then injected with 150 larvae (L1-T. spiralis) per os.Chronic inflammation was caused by infection of treated or untreated mice with T. spiralis parasite. After 14 days post-infection all mice developed a chronic inflammatory response. Mice fed with a B6-deficient diet showed a significant decrease in the number of cysts found in the diaphragm when compared to mice treated with normal diet. In addition, in all mice treated with vitamin B6-deficient diet plus 4-DPD the average body weight was significantly lower, compared to the mice on normal diet in all weeks examined. Moreover, in sections of the diaphragm, masseter and miocardium muscles, the infiltration of inflammatory cells, such as macrophages, lymphocytes, and eosinophils were more intense in untreated mice compared to those fed a vitamin B6-deficient diet.These results show that BALB/c mice infected with T. spiralis and fed a vitamin B6-deficient diet plus the vitamin B6 antagonist, 4-DPD, prolong the time of invasion of the larvae in the muscle cells, influence the recruitment of inflammatory cells and the intensity of the inflammatory reaction compared to infected untreated mice (control)     

Effects of blood products on inflammatory response in endothelial cells in vitro

Background

Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products.

Methods

The inflammatory response from pre-activated (endotoxin-stimulated) and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC), platelet concentrates (PC) and fresh frozen plasma (FFP) was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated.

Results

Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product.

Conclusion

Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells.     

Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity

Background

Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.

Principal Findings

Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.

Conclusion

Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.     

Induction of cytokine expression in rat post-ischemic sinoatrial node (SAN)

The aim of this study was to determine the spatial and temporal expression of various pro-inflammatory cytokines in the peri-sinoatrial nodal area after atrial infarction. Rats were subjected to permanent atrial infarction, in particular, sinoatrial node (SAN) infarction and sacrificed at various time points up to 7 days. Real-time polymerase chain reaction analysis demonstrated that mRNA levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta, interleukin-6, and transforming growth factor beta 1 (TGF-beta(1)) were upregulated in the peri-sinoatrial nodal area after atrial infarction. Immunostaining for TNF-alpha and TGF-beta(1) proteins revealed that both cytokines were expressed persistently up to 7 days after atrial infarction around the peri-sinoatrial nodal area. Furthermore, the infiltrating inflammatory cells immunoreactive for both cytokines were predominant within the infarct SAN. In situ hybridization analysis showed that TNF-alpha gene expression was enhanced in the inflammatory cells and myocardium within the peri-sinoatrial nodal area in response to the infarction. These results provide evidence for the local expression of cytokines in the post-ischemic peri-sinoatrial nodal area, suggesting that the upregulation of the cytokines might be associated with the atrial arrhythmia observed after acute myocardial infarction.     

Paragonimus kellicotti infection in wild carnivores in southwestern Ontario: II. Histopathologic features.

Pulmonary lesions associated with naturally acquired Paragonimus kellicotti infection were studied in mink (Mustela vison), striped skunks (Mephitis mephitis), red foxes (Vulpes vulpes) and a coyote (Canis latrans). In ,ink a fibrous capsule was formed around mature flukes in dilated bronchioles or bronchi, and there was mild focal interstitial pneumonitis adjacent to fluke eggs in alveoli and migrating parasites. A thick wall, infiltrated heavily with mononuclear cells and eosinophils, surrounded mature P. kellicotti in skunks and an extensive inflammatory reaction was found around fluke eggs. In red foxes the wall was thin, hemorrhagic and contained little collagen; necrosis was associated with migrating parasites. Thick capsules formed by marked fibroplastic changes in the lamina propria of affected bronchi were found in the coyote. In raccoons with pleural adhesions massive fibroplasia with eosinophil infiltration beneath the pulmonary pleura suggested a reaction to a migrating parasite entering the lung from the thoracic cavity. It was thought that immature P. kellicotti may have caused the lesion.     

Myotoxicity induced by an acidic Asp-49 phospholipase A(2) isolated from Lachesis muta snake venom. Comparison with lysophosphatidylcholine

In a previous report we showed that Lachesis muta crude venom displays potent indirect hemolytic activity and myotoxicity when injected into mice. Then, a phospholipase A(2) (PLA(2)) (LM-PLA(2)-I) responsible for these activities was isolated. More recently, a catalytically active isoenzyme (LM-PLA(2)-II) with molecular mass of 18 kDa and isoeletric point at pH 5.4 was isolated from the same snake venom. LM-PLA(2)-II inhibited ADP- and collagen-induced platelet aggregation as well as induced a potent paw edema reaction in rats. Here we show that LM-PLA(2)-II induced myotoxic effects both in vitro characterized by an increase on the rate of creatine kinase (CK) release from isolated mice extensor digitorum longus (EDL) muscles and in vivo by increasing plasma CK activity of injected mice. Histological analysis showed an intense damage in muscle cells injected with LM-PLA(2)-II. It was also shown that exogenous lysophosphatidylcholine (lyso-pc) behaved as a typical myotoxin damaging muscle cells, producing myonecrosis characterized by local infiltration of inflammatory cells similarly to that observed for LM-PLA(2)-II. Hemorrhage and lethal effects were not observed neither with LM-PLA(2)-II nor lyso-pc. As previously observed for other biological activities, pretreatment of LM-PLA(2)-II with p-bromophenacyl bromide (p-BPB) or acetic anhydride abolished all the enzyme's actions. The data confirms that biological activities displayed by LM-PLA(2)-II, including the myotoxic effects reported here, are all dependent on its enzymatic activity where the product formed (lyso-pc) may play an important function on such myotoxicity.     

Inflammatory cell distribution in guinea pig airways and its relationship to airway reactivity.

Although airway inflammation and airway hyperreactivity are observed after allergen inhalation both in allergic humans and animals, little is known about the mechanisms by which inflammatory cells can contribute to allergen-induced airway hyperreactivity. To understand how inflammatory cell infiltration can contribute to airway hyperreactivity, the location of these cells within the airways may be crucial Using a guinea pig model of acute allergic asthma, we investigated the inflammatory cell infiltration in different airway compartments at 6 and 24 h (i.e. after the early and the late asthmatic reaction, respectively) after allergen or saline challenge in relation to changes in airway reactivity (AR) to histamine. At 6 h after allergen challenge, a threefold (p < 0.01) increase in the AR to histamine was observed. At 24 h after challenge, the AR to histamine was lower, but still significantly enhanced (1.6-fold, p < 0.05). Adventitial eosinophil and neutrophil numbers in both bronchi and bronchioli were significantly increased at 6 h post-allergen provocation as compared with saline (p < 0.01 for all), while there was a strong tendency to enhanced eosinophils in the bronchial submucosa at this time point (p = 0.08). At 24h after allergen challenge, the eosinophilic and neutrophilic cell infiltration was reduced. CD3+ T lymphocytes were increased in the adventitial compartment of the large airways (p < 0.05) and in the parenchyma (p < 0.05) at 24h post-allergen, while numbers of CD8+ cells did not differ from saline treatment at any time point post-provocation. The results indicate that, after allergen provocation, inflammatory cell numbers in the airways are mainly elevated in the adventitial compartment. The adventitial inflammation could be important for the development of allergen-induced airway hyperreactivity.     

Cholesterol lowering and the vessel wall: new insights and future perspectives.

The basis for most acute coronary events is either rupture or fissuring of unstable atherosclerotic plaques with subsequent thrombosis leading to coronary artery occlusion. The development of atherosclerotic plaques takes several decades, but the mechanical features determining its stability and the risk of rupture can change very rapidly depending on a number of internal factors. Unstable plaques have a large lipid core, a thin overlying fibrous cap and an abundance of inflammatory cells. The most important factor determining the plaque stability is the plasma level of atherogenic LDL particles. Increased levels of these particles cause endothelial dysfunction with impaired vasodilatation capacity and prevalence of vasoconstriction, maintain inflammatory infiltration of the plaque, impair the strength of the fibrous cap and facilitate aggregation and coagulation. Effective lowering of plasma cholesterol by pharmacological and non-pharmacological means can revert most of these processes and increase the plaque's mechanical stability within several hours to days. Lipid lowering therapy can therefore decrease the risk of acute coronary events within a very short space of time. Thus a radical decrease in lipid levels, along with modification of other risk factors, may become the cornerstone for treatment of acute coronary syndromes, in addition to being an effective treatment in primary and secondary prevention of coronary heart disease (CHD).