Peak Inflammatory Response Research Articles

Effect of anti-inflammatory drugs on pleurisy induced by latex of Calotropis procera in rats

In present study, we have characterized the inflammation induced by latex of Calotropis procera in the rat pleurisy model and evaluated the effect of various inhibitors of inflammatory mediators. Injection of dried latex (DL) into the pleural cavity elicited an acute inflammatory response characterized by protein rich fluid accumulation and leucocyte (polymorphonuclear cells, and mononuclear cells) infiltration in the pleural cavity. The peak inflammatory response was obtained at 6 h when the fluid volume, protein concentration and cell infiltration were maximum. All these parameters were attenuated by phenylbutazone (PBZ), celecoxib, dexamethasone, cyproheptadine and chlorpheniramine. All these drugs were also effective in inhibiting the production of prostaglandin E 2 (PGE 2). Of all the drugs tested, dexamethasone was most effective in inhibiting DL induced pleurisy. The results clearly indicate that prostaglandins (PGs) and biogenic amines play a key role in the development of pleurisy induced by DL and it serves as a model to evaluate drugs inhibiting cellular influx associated with inflammatory response.

Early objective assessment of intraocular inflammation after phacoemulsification cataract surgery

Purpose: To evaluate the time course of blood–aqueous barrier (BAB) disturbance in the early period after small-incision cataract surgery. Setting: Department of Ophthalmology, Vienna University, Vienna, Austria. Methods: In a prospective study, 15 eyes of 15 patients with age-related cataract had small-incision cataract surgery by phacoemulsification with intraocular lens implantation. Care was taken to minimize trauma to the uvea during surgery. Postoperative inflammation was assessed by measuring aqueous flare and cell count with a laser flare–cell meter. Postoperative measurements were performed hourly for the first 6 hours, every 2 hours until 12 hours, every 4 hours until 40 hours, and every 8 hours until 56 hours. Results: The time course of aqueous flare and cell count differed significantly among patients. The peak inflammatory response in most cases was 1 hour after surgery, with the response decreasing thereafter. The pattern of the time course was classified into subgroups defined by the presence and size of an initial spike immediately after surgery and the intensity of the subsequent inflammatory reaction. A slight increase in flare and cells was seen in the morning hours of the first postoperative day. Conclusions: Acute BAB disturbance within the first 48 hours after small-incision cataract surgery showed high interpatient variability. However, many differences were not detectable 1 day after surgery.

Immunoregulatory role of ocular macrophages: the macrophages produce RANTES to suppress experimental autoimmune uveitis.

Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages play a crucial role in the generation of tissue damage in EAU. In fact, several chemokines are actually produced in the inflamed eye. The aim of this study was to elucidate the role of ocular macrophage-derived chemokines in EAU. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein peptide 1-20, and the EAU severity was scored at multiple time points based on microscopic fundus observations (retinal vascular dilatation and exudates) and histological examinations. The peak inflammatory response was observed 1 wk (day 16) after the beginning of macrophage infiltration to the eye (day 9). Ocular-infiltrating cells were enriched or depleted of macrophages by magnetic beads and analyzed by real-time RT-PCR for chemokine mRNA production. We found that only the macrophage-enriched cells from the eye produced RANTES, and thus proposed that macrophage-derived RANTES facilitated the ocular inflammations. In contrast to our postulate, neutralization of RANTES by specific Ab in vivo on days 9 and 13 exacerbated EAU. We also found that the ratio of ocular CD4/CD8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. In conclusion, our data provide insight into the immunoregulatory role of macrophages and RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines cause local inflammation, since RANTES produced by ocular macrophages appears to suppress EAU.

Vanadium‐induced apoptosis and pulmonary inflammation in mice: Role of reactive oxygen species

Pulmonary exposure to metals and metal-containing compounds is associated with pulmonary inflammation, cell death, and tissue injury. The present study uses a mouse model to investigate vanadium-induced apoptosis and lung inflammation, and the role of reactive oxygen species (ROS) in this process. Aspiration of the pentavalent form of vanadium, V (V), caused a rapid influx of polymorphonuclear leukocytes into the pulmonary airspace with a peak inflammatory response at 6 h post-exposure and resolution by 72 h. During this period, the number of apoptotic lung cells which were predominantly neutrophils increased considerably with a peak response at 24 h accompanied by no or minimum necrosis. After 24 h when the V (V)-induced inflammation was in the resolution phase, an increased influx of macrophages and engulfment of apoptotic bodies by these phagocytes was observed, supporting the role of macrophages in apoptotic cell clearance and resolution of V (V)-induced lung inflammation. Electron spin resonance (ESR) studies using lavaged alveolar macrophages showed the formation of ROS, including O(2)(*-), H(2)O(2), and (*)OH radicals which were confirmed by inhibition with free radical scavengers. The mechanism of ROS generation induced by V (V) involved the activation of an NADPH oxidase complex and the mitochondrial electron transport chain. The ROS scavenger, catalase (H(2)O(2) scavenger), effectively inhibited both lung cell apoptosis and the inflammatory response, whereas superoxide dismutase (SOD) (O(2)(*-) scavenger) and the metal chelator, deferoxamine (inhibitor of (*)OH generation by Fenton-like reactions) had lesser effects. These results indicate that multiple oxidative species are involved in V (V)-induced lung inflammation and apoptosis, and that H(2)O(2) plays a major role in this process.

Eotaxin represents the principal eosinophil chemoattractant in a novel murine asthma model induced by house dust containing cockroach allergens.

Asthma represents a serious health problem particularly for inner city children, and recent studies have identified that cockroach allergens trigger many of these asthmatic attacks. This study tested the concept that asthma-like pulmonary inflammation may be induced by house dust containing cockroach allergens. An aqueous extract was prepared from a house dust sample containing endotoxin and high levels of cockroach allergens. BALB/c mice were immunized with the house dust extract (HDE) and received two additional pulmonary challenges. Bronchoalveolar lavage (BAL) eosinophil counts and eotaxin levels were significantly increased in immunized mice exposed to the HDE, whereas neutrophils were the predominant BAL inflammatory cell in the unimmunized mice. Kinetics studies in immunized mice demonstrated a peak pulmonary inflammatory response 48 h after the last challenge. The allergic response in this model was further confirmed by histological and physiological studies demonstrating a significant influx of eosinophils and lymphocytes in the peribronchial area, and severe airway hyperreactivity through whole-body plethysmography. The specificity of the response was established by immunizing with HDE and challenging with purified cockroach allergen, which induced pulmonary eosinophilia and airway hyperreactivity. Ab inhibition of eotaxin significantly inhibited the number of BAL eosinophils. These data describe a novel murine model of asthma-like pulmonary inflammation induced by house dust containing endotoxin and cockroach allergens and further demonstrate that eotaxin represents the principal chemoattractant for the recruitment of the pulmonary eosinophils.

Neutrophil apoptosis during the development and resolution of oleic acid-induced acute lung injury in the rat.

The oleic acid (OA) model of acute lung injury in rats is characterized by a massive and rapid influx of polymorphonuclear neutrophils (PMN) within 1 h, with a peak inflammatory response at 4 h and resolution by 72 h. We hypothesized that PMN apoptosis is involved in the resolution of OA-induced acute lung injury. To test this hypothesis, healthy adult Fischer 344 rats were given 30 microl OA in 0.1% bovine serum albumin (BSA) intravenously; controls were given BSA alone and killed at 1, 4, 24, and 72 h after OA to obtain bronchoalveolar lavage fluid (BALF) and lung tissue. Cell pellets from BALF and formalin-fixed, paraffin-embedded tissue section samples were processed for terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) to identify apoptotic cells. Propidium iodide was used to counterstain nuclei. Percentage of nuclei undergoing apoptosis was counted under a fluorescent microscope. Control rats showed only resident alveolar macrophages (AM) in the BALF with no apoptosis. At the peak of injury, 1 h and 4 h after OA injection, we observed a massive PMN response without any evidence of apoptosis. At 24 h, when the OA injury is clinically and histologically in early resolution, we observed intense apoptosis of PMN nuclei along with evidence of apoptotic bodies in the cytoplasm of AM. Some of the AM also showed apoptotic nuclei at 72 h. Similar observations were made in the lung tissue sections. The results of the TUNEL assay were confirmed by DNA ladders and electron microscopy. We conclude that apoptosis of PMN and clearance by AM is an important mechanism in resolution of OA- induced acute lung injury.

A comparison of wound healing after epithelial resection by ultrasonic surgical aspiration and ablation by the carbon dioxide laser

The ultrasonic surgical aspirator (USA) offers unique surgical options in the treatment of vulvar intraepithelial diseases. Clinical observations have shown results that equal those achieved with the use of the carbon dioxide laser with regard to patient satisfaction and incidence of recurrent disease. The purpose of this study was to compare the USA to the carbon dioxide laser in the laboratory with respect to ease of use, adequacy of epithelial removal, amount of tissue damage, and timing of wound healing. The backs of ten Hartley guinea pigs were marked with eight 1-cm 2 patches placed 2 cm apart. Each instrument was used to ablate or resect the area within four patches on each animal's back to the level of the middermis (0.5–1.0 mm). At time intervals from 0 hr to 28 days, the eight 1-cm patches were removed and evaluated histologically. The USA was easier to control and maintain within the 1-cm 2 patch than the laser was. On histologic evaluation, the USA demonstrated less adjacent epithelial damage. The peak inflammatory response, depth of collagen denaturation, reepithelialization, and healing at 28 days were similar in both groups. The study indicates that the ultrasonic surgical aspirator is effective in epithelial removal and allows rapid wound healing with minimal scarring.

Clearance of Experimental Vitreous Hemorrhage After Panretinal Cryotherapy Is Related to Macrophage Influx

We investigated the effect of panretinal cryotherapy on blood clearance and on the inflammatory cellular response in rabbit eyes with experimental vitreous hemorrhage. Eyes treated with cryotherapy demonstrated less extensive vitreous opacity and more rapid clearance of blood than untreated eyes. The peak inflammatory cellular response measured by counts or radiolabeled cells in the optic nerve was 2.5 times greater in the cryotherapy-treated eyes. Panretinal cryotherapy may promote the clearance of vitreous hemorrhage by stimulating the influx of increased numbers of phagocytic inflammatory cells.

Phlogistic and Chemotactic Activities of Alveolar Hydatid Cyst Antigen

Alveolar hydatid cyst antigen (AHCA) absorbed with Sepharose-coupled anti-mouse Ig or its Sephacryl S-300 fractions was assayed for phlogistic/chemotactic and amyloidogenic properties in C57BL/6J mice. The in vivo and in vitro biological properties of the antigen were assessed by intradermal or intraperitoneal routes in mice or in Boyden chambers, respectively. In both these assays the chemotactic activity of the antigen was found to be dose dependent. A single intradermal injection of the antigen, containing 35 or 70 micrograms protein, showed a peak inflammatory cell response in the dermal layers at 6 hr. Neutrophils were the dominant cellular infiltrates and the number of monocytoid cells, except at 24 hr, remained relatively low. Antigen concentrations ranging from 1 to 200 micrograms protein per Boyden chamber showed peak neutrophilic and monocytoid cell responses with 100 micrograms of the antigen. We therefore conclude that intense inflammatory response and amyloidogenesis in alveolar hydatid cyst-infected murine hosts are directly attributable to the parasite antigen.