Development Of Acute Inflammation Research Articles

Serum Clusterin Concentration and Its Glycosylation Changes as Potential New Diagnostic Markers of SARS-CoV-2 Infection and Recovery Process.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Glycoprotein clusterin (CLU) has many functions such as phagocyte recruitment, complement system inhibition, apoptosis inhibition, hormone and lipid transport, as well as in the immune response. The study aimed to assess the changes in CLU concentrations and the profile and degree of CLU glycosylation between patients with severe COVID-19, convalescents, and healthy subjects (control). The profile and degree of serum CLU N-glycosylation were analyzed using lectin-ELISA with specific lectins. CLU concentrations were significantly lower and relative reactivities of CLU glycans with SNA (Sambucus nigra agglutinin) were significantly higher in severe COVID-19 patients in comparison to convalescents and the control group. The relative reactivities of CLU glycans with MAA (Maackia amurensis agglutinin), together with relative reactivity with LCA (Lens culinaris agglutinin), were also significantly higher in patients with severe COVID-19 than in convalescents and the control group, but they also significantly differed between convalescents and control. The development of acute inflammation in the course of severe COVID-19 is associated with a decrease in CLU concentration, accompanied by an increase in the expression of α2,3-linked sialic acid, and core fucose. Both of these parameters can be included as useful glycomarkers differentiating patients with severe COVID-19 from convalescents and the control group, as well as convalescents and healthy subjects.

Extracellular DNA in blood: an index of <i>in vivo</i> inflammatory response

Increased concentration of cell-free DNA (cfDNA) in the circulating blood of humans and animals is a sign of inflammatory conditions and a distinctive characteristic of various pathophysiological processes in the body. The aim of the present study was to investigate the possible role of tumor necrosis factor (TNFα) in changes of cfDNA contents in peripheral blood as a response to experimentally induced systemic inflammation.We used 40 female hybrid mice (C57Bl/6xDBA/2) F1 at the age of 6-8 weeks. The concentration of cfDNA and its individual fractions was determined using a PicoGreen fluorescent dye. The dynamics of inflammatory process was evaluated after 4, 8, 11 and 24 hours following LPS injection. A significant increase in the blood plasma cfDNA levels was shown under the action of E. coli lipopolysaccharide (LPS), along with simultaneous decreased levels of cfDNA, associated with cell surface. The ratio of cell surface-bound cfDNA to the total cfDNA contents was reduced in dose-dependent manner as early as 4 hours after LPS injection to the animals, thus allowing us to consider this ratio a characteristic sign of netosis of neutrophilic granulocytes during the development of acute inflammation. The described effects are significantly suppressed with co-injection of recombinant TNFα neutralizing protein along with LPS, whereas increased intake of neutrophils in the tissues is determined by some other factors which are not directly related to the production of this cytokine.Based on the obtained data, we proposed a following hypothesis: induction of netosis by inflammatory stimuli causes an increase in the concentration of cfDNA in blood plasma not only due to de novo emerging extracellular DNA by neutrophil netosis, but also by the release of distinct cfDNA fraction that was previously firmly bound to cell membranes in multiple body tissues under the action of proteases released during netosis.

Problems and prospects for the use of stem cells in transplantation

The problems of organ and tissue transplantation are the lack of organs for transplantation and the rejection of transplants. Therefore, the issue of obtaining organs and tissues for transplantation with stem cells is being studied. Although this idea is promising, it is associated with many problems. To do this, you need to use several populations of cells on a substrate with a complex composition of nutrient environments: nutrients, growth factors, oxygen, regulatory factors. Intercellular interaction is provided by the factors they secrete, or it occurs directly with intercellular contact. This contributes to the fact that stem cells in test tubes can differentiate into other types of tissues and maintain their biological activity indefinitely, which they cannot in vivo. This approach of tissue engineering provides the possibility of obtaining whole organs for implantation. However, technical problems are associated with increased cell adhesion to plastic, the presence of a universal basis for cell nutrition, which can contain more than 100 components. There is a possibility of contamination, which can lead to serious errors in the experiment. Stem cells must have distinct mutational properties and the ability to restore telome cells. Prolonged use of the same nutrient medium can lead to genetic changes and significantly alter the physiological properties of cells. Cryopreservation can be an important aspect of the solution. The goal of tissue bioengineering is to create whole artificial organs, or at least areas of organized tissue that could be transplanted to patients. Currently, such operations are relatively simple for tissues such as artificial skin consisting of epidermal and fibroblast layers, or small cartilage implants obtained in vitro. Several cell types in stable shape are planned to be used in one environment. In this case, one type of cell can be replaced by another. This stability is provided by a variety of secreted factors by different types of cells that ensure their vitality. Decellularization removes all components involved in immune rejection of grafts, so this raises the prospect of creating an unlimited supply of organs for transplantation. However, acute reactions can develop associated with the participation of dendritic cells, macrophages, neutrophils, natural killers. Starting from the moment of transplantation, conditions for immune rejection are created, arising as a result of surgery with the development of acute inflammation. The intensity of immune reactions against the graft largely depends on the degree of non-conformity of alleles of the main complex of histocompany capacity of the donor and recipient. This match is studied using a variety of methods, including the use of antibodies or sequencing of deoxyribonucleic acid.

Источники проникновения бактерий в почку (обзор литературы. Часть II)

Kidney and upper urinary tract infections are a serious general medical problem that is the subject of ongoing experimental and clinical research. However, etiological factors and the pathophysiological mechanisms of acute infectious renal inflammation are poorly understood. This also applies to the problem of sources of bacterial penetration into the kidney. The existing hypotheses on this score have blank spots. This review comprehensively examines the pathways of invasion of microorganisms into the kidney, causing the development of acute inflammation in it. The proofs in favour of the existing views and their criticism are presented. Also, weaknesses in the inference system are determined.

Frontline Science: The expression of integrin αD β2 (CD11d/CD18) on neutrophils orchestrates the defense mechanism against endotoxemia and sepsis.

Neutrophil-macrophage interplay is a fine-tuning mechanism that regulates the innate immune response during infection and inflammation. Cell surface receptors play an essential role in neutrophil and macrophage functions. The same receptor can provide different outcomes within diverse leukocyte subsets in different inflammatory conditions. Understanding the variety of responses mediated by one receptor is critical for the development of anti-inflammatory treatments. In this study, we evaluated the role of a leukocyte adhesive receptor, integrin αD β2 , in the development of acute inflammation. αD β2 is mostly expressed on macrophages and contributes to the development of chronic inflammation. In contrast, we found that αD -knockout dramatically increases mortality in the cecal ligation and puncture sepsis model and LPS-induced endotoxemia. This pathologic outcome of αD -deficient mice is associated with a reduced number of monocyte-derived macrophages and an increased number of neutrophils in their lungs. However, the tracking of adoptively transferred fluorescently labeled wild-type (WT) and αD-/- monocytes in WT mice during endotoxemia demonstrated only a moderate difference between the recruitment of these two subsets. Moreover, the rescue experiment, using i.v. injection of WT monocytes to αD -deficient mice followed by LPS challenge, showed only slightly reduced mortality. Surprisingly, the injection of WT neutrophils to the bloodstream of αD-/- mice markedly increased migration of monocyte-derived macrophage to lungs and dramatically improves survival. αD -deficient neutrophils demonstrate increased necrosis/pyroptosis. αD β2 -mediated macrophage accumulation in the lungs promotes efferocytosis that reduced mortality. Hence, integrin αD β2 implements a complex defense mechanism during endotoxemia, which is mediated by macrophages via a neutrophil-dependent pathway.

860 - Can S. haemolyticus and P. niger causing the development of acute inflammation in the prostate?

860 - Can S. haemolyticus and P. niger causing the development of acute inflammation in the prostate?

Endodontic flare-ups: A review

Endodontic treatment can stimulate potential symptoms such as pain and swelling during or after the treatment known as the Endodontic flare-ups which is a nightmare for both Dentist and Patients. Its incidence can vary from 1.4 to 50. The multi-causal origin of these flare-ups include the microbial factors the patient factors and the treatment factors. Among these conceivably micro-organisms play a major role. The principal reason for the inter-appointment pain is the development of acute inflammation in the peri-radicular tissue region in response to any irritation extending from the root canal system. Considering these situations preventive measures and treatment strategies against these flare ndashups has been proposed. Having a proficient knowledge about the etiologic factors and the management of these flare ndashups can help in reducing the occurrence of this abominable event.

Probable Mechanisms Involved in Immunotoxin Mediated Capillary Leak Syndrome (CLS) and Recently Developed Countering Strategies.

Antibody-toxin fused agents or immunotoxins, are a newly engineered class of cytotoxic agents consisting of a bacterial or plant toxin moiety hooked up either to a monoclonal antibody or a specific growth factor. Nevertheless, acquiring a full potency in clinic is mostly restricted due to the Capillary leak syndrome (CLS), a serious immune provoked, life-threatening side effect, subsequent to the endothelial damage, resulting in fluid escape from the bloodstream into tissues including lungs, muscle and brain, developing organ failure and eventually death. Proposed underlying mechanisms include direct damage to endothelial cells, acute inflammation, Lymphokine-activated killer (LAK) cells engagement, alteration in cell-cell/cell-matrix connectivities and cytoskeletal dysfunction. Very poor biodistribution and heterogeneous extravasation pattern in tumor site result in accumulation of ITs close to the extravasation site, gradual toxin release and initiation of nearby endothelial cells lysis, secretion of pro-inflammatory cytokines, development of acute inflammation and engagement of Lymphokine-activated killer (LAK) cells. Intrinsic immunogenicity of applied toxin moiety is another important determinant of CLS incidence. Toxins with more intrinsic immunogenicity possess more probability for CLS development. Recently, development of new generations of antibodies and mutated toxins with conserved cytotoxicity has partly tapered risk of CLS development. Here, we describe probable mechanisms involved in CLS and introduce some of the recently applied strategies for lessening incidence of CLS as much as possible.

ANTI-INFLAMMATORY EFFECT OF ELETTARIA CARDAMOM OIL ON CARRAGEENAN-INDUCED PAW EDEMA USING RATS BASED ON TUMOR NECROSIS FACTOR α, INTERLEUKIN 6, AND INTERLEUKIN 1 LEVELS IN SERUM

Objective: In this study, we evaluated the anti-inflammatory effect of Elettaria cardamom oil and the underlying mechanism using in vivo models of inflammation.Methods: Male Sprague–Dawley rats, 4-6 weeks old, weighing 120-130 gms are used for the study. The anti-inflammatory study of E. cardamom oil was studied by injecting 0.1 ml of 1% carrageenan to the subplantar region of the right hind paw of rats. The development of acute inflammation was measured at the end of every 1st, 2nd, 3rd, 4th, 5th, and 6th h using plethysmometer.Results: As results from the above study, E. cardamom oil at a dose of 0.175 ml/kg was less significant than that of E. cardamom oil at a dose of 0.280 ml/kg when given orally. A p<0.05 shows a significant decrease in paw edema. It also reduced the levels of pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL) 1, and IL 6 levels in the serum. The histopathology results also showed a significant reduction of congested blood vessels with no marked impression for inflammation.Conclusion: E. cardamom oil possesses anti-inflammatory activity in dose-dependent manner as they inhibit the levels of pro-inflammatory cytokines.

Analysis of complications of percutaneous X-Ray endoscopic surgical operations of patients with urolithiasis and nephrolithiasis with a single functioning kidney

The presented article focuses on the important matters of development of intraoperative and postoperative complications in patients with urolithiasis undergoing percutaneous operative treatment for coral calculus of a solitary or sole functioning kidney. Complications of percutaneous X-ray-endoscopic operations in these patients always require careful medical and diagnostic approach, as they can lead to oppression of an already impaired solitary kidney function and, as a consequence, can have life-threatening nature. They are divided into two groups: intraoperative and postoperative complications. Intraoperative complications include: bleeding, damage of the renal pelvis in the course of creating of puncture access, perforation of internal organs, loss of stroke. Postoperative complications include: development of acute inflammation in a single kidney, bleeding, urinoma or hematoma development, progression of renal failure, leave of residual concretions, organ loss. There is a sufficient amount of data on the development of complications after percutaneous endoscopic surgeries in the literature, but very few works are devoted to a solitary kidney matter. The object of this study was the group of patients with urolithiasis, coral nephrolithiasis by a solitary or a single functioning kidney, who were on treatment in the urology department of the N.I. Pirogov City Clinical Hospital No. 1 from January 2007 to July 2014. All patients underwent percutaneous operative treatment for the removal of coral calculi.

Changes in toll-like receptor (TLR)4–NFκB–IL1β signaling in male gout patients might be involved in the pathogenesis of primary gouty arthritis

We undertook this study to determine whether the altered toll-like receptor (TLR)4-nuclear factor κB (NFκB)-interleukin1β (IL1β) signaling in peripheral blood of gout patients could provide insights into the pathogenesis of primary gouty arthritis (GA). TLR4 mRNA, TLR4 and NFκBp65 proteins expression and IL1β production were measured in 52 acute GA (AGA) and 34 non-acute GA (NAGA) male patients and 78 male healthy subjects (HC). NFκBp65 transcriptional activity and IL1β production were measured after TLR4 inhibition with anti-TLR4 antibody in peripheral whole blood from 13 AGA patients. The TLR4, NFκBp65 and IL1β expression was significantly increased in the AGA group than those in the NAGA or HC group (P<0.05, respectively), also the levels were higher in the NAGA group comparing with those in the HC group (P<0.05, respectively). Furthermore, moderate positive correlations were observed between concentration of uric acid and the TLR4 mRNA level, serum IL1β production (r=0.649, 0.616), and strong positive correlation was observed between TLR4 mRNA level and serum IL1β (r=0.848) in 52 AGA patients. On the other hand, NFκBp65 level and IL1β production were dramatically reduced after TLR4 blockade with anti-TLR4 antibody in peripheral blood from the AGA patients (P<0.05, respectively). TLR4-NFκB-IL1β signaling might play a crucial role in the development of acute inflammation in primary gout patients.

Galectin-9 and inflammation

Galectin-9 is a novel eosinophil chemoattractant,which belong to Galectin family.Galectin-9exhibits a variety of biological functions,such as cell differentiation,maturation,adhesion and aggregation,cell chemotaxis,activity,and cell death.Galectin-9 may play important roles in the development of acute inflammation as well as chronic inflammation associated with allergies,autoimmune diseases,infectious processes.This review summarizes the advances in Galectin-9 study. Key words: Galectins; Galectin-9 ; Inflammation

Galectins: regulators of acute and chronic inflammation

Galectins, beta-galactoside-binding animal lectins, are differentially expressed by various immune cells as well as a wide range of other cell types. Extracellularly, galectins are able to exhibit bivalent or multivalent interactions with cell-surface glycans on various immune cells and exert various effects. These include cytokine and mediator production, cell adhesion, apoptosis, and chemoattraction. In addition, they can form lattices with cell-surface glycoprotein receptors, resulting in modulation of receptor functions, including clustering and endocytosis. Intracellularly, galectins can participate in signaling pathways and modulate biologic responses. These include apoptosis, cell differentiation, and cell migration. Thus, a large body of literature indicates that galectins play important roles in the immune and inflammatory responses through regulating the homeostasis and functions of immune cells. The use of mice deficient in individual galectins has provided additional evidence for the contributions of these proteins to these responses. Current research indicates that galectins play important roles in the development of acute inflammation as well as chronic inflammation associated with allergies, autoimmune diseases, atherosclerosis, infectious processes, and cancer. Thus, recombinant proteins or specific galectin inhibitors may be used as therapeutic agents for inflammatory diseases.

The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation

The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study was to evaluate the role of the PPAR-alpha receptor on the development of acute inflammation. To address this question, we used two animal models of acute inflammation (carrageenan-induced paw edema and carrageenan-induced pleurisy). We report here that when compared with PPAR-alpha wild-type mice, PPAR-alpha knockout mice (PPAR-alphaKO) mice experienced a higher rate of the extent and severity when subjected to carrageenan injection in the paw edema model or to carrageenan administration in the pleurisy model. In particular, the absence of a functional PPAR-alpha gene in PPAR-alphaKO mice resulted in a significant augmentation of various inflammatory parameters (e.g., enhancement of paw edema, pleural exudate formation, mononuclear cell infiltration, and histological injury) in vivo. Furthermore, the absence of a functional PPAR-alpha gene enhanced the staining (immunohistochemistry) for FAS ligand in the paw and in the lung and the expression of tumor necrosis factor alpha and interleukin-1beta in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-alphaKO mice strongly suggests that a PPAR-alpha pathway modulates the degree of acute inflammation in the mice.

Protective effects of preischemic treatment with pioglitazone, a peroxisome proliferator-activated receptor-gamma ligand, on lung ischemia-reperfusion injury in rats.

Lung injury induced by ischemia-reperfusion is the main cause of early graft failure after lung transplantation, which may result from oxygen-free radicals, inflammatory cytokine production, and polymorphonuclear leukocyte accumulation into the interstitium, resulting in severe lung edema. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to the nuclear receptor superfamily and has an anti-inflammatory effect by preventing the activation of transcription factors such as nuclear factor-kappaB (NF-kappaB). NF-kappaB regulates the expression of many genes of early response products in the development of acute inflammation. We examined the effects of pioglitazone, a synthetic ligand of PPAR-gamma, against lung ischemia-reperfusion injury in rats. The left lungs of male Wistar rats were rendered ischemic for 90 min and then reperfused for 2 h. Treated animals received pioglitazone (10 mg/kg) 2 h before induction of ischemia. Lung injury was quantified in terms of lung microvascular permeability (Evans blue dye extravasation), tissue lipid peroxidation (thiobarbituric acid reactive substances), and tissue polymorphonuclear leukocyte accumulation (myeloperoxidase activity). The tissue concentrations of tumor necrosis factor-alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were also measured. Statistical analyses were performed by one-way analysis of variance, followed by Sheffe's multiple comparison test. The lung vascular permeability in pioglitazone-treated animals was reduced by 55% of the increase of Evans blue dye extravasation relative to control animals (P=0.003). The protective effects of pioglitazone treatment were correlated with the reduction by 79% of the increase of thiobarbituric acid reactive substances (P=0.045) and the reduction by 58% of myeloperoxidase activity increase (P<0.001). The production of TNF-alpha was reduced by 63% of the increase (P<0.001) and the reduction of CINC-1 was 45% (P<0.001). Pioglitazone did not affect the lung in the sham animals. Pioglitazone treatment before ischemia attenuated lung ischemia-reperfusion injury in rats. The mechanism of these protective effects involves inhibition of the production of proinflammatory cytokines, polymorphonuclear leukocyte accumulation, and tissue lipid peroxidation, resulting in reduced lung edema.

Impairment of inflammatory response in adult rats submitted to maternal undernutrition during early lactation: role of insulin and glucocorticoid.

Early nutritional environment may program permanent metabolic alterations, predisposing to later diseases. We have investigated the interference of maternal malnutrition during lactation with the development of acute inflammation in adult rats. Adult rats, offspring of dams fed with either protein-free diet (UN group) or 22% protein diet (C group) during the first 10 days of lactation, were submitted to pleurisy with carrageenan (500 microg/cavity). Pleural edema, neutrophil migration and ICAM expression, were evaluated 4 h after and correlated with alterations in plasma insulin and corticosterone. Leukocyte-endothelium interactions were evaluated by intravital microscopy 1 h after inflammation. Compared to controls, UN rats showed a decrease in pleural edema formation (50%), neutrophil migration (50%), endothelial ICAM-1 expression on pulmonary tissue, and impairment in leukocyte adhesion (50%) and migration (80%) through endothelium. Circulating insulin was lower (42%) and corticosterone was higher (34%) in UN, compared to controls. Pre-treatment of UN with insulin (5 IU/day) or RU486 (20 mg/kg/day), inhibitor of glucocorticoid receptor, restored leukocyte functions and ICAM-1 expression. Postnatal maternal malnutrition, programming for permanent alterations in insulin and glucocorticoid secretion in progeny, that were unable to properly mount an inflammatory response, probably predisposes to chronic diseases in adult life.

Inducible Nitric Oxide Synthase—Knockout Mice Exhibit Resistance to Pleurisy and Lung Injury Caused by Carrageenan

In the present study, we investigated the role of inducible (or type 2) nitric oxide synthase (iNOS) in the development of acute inflammation by comparing the responses in wild-type mice (WT) and mice lacking (knockout [KO]). When compared with carrageenan-treated iNOS-WT mice, iNOS-KO mice that had received carrageenan exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung myeloperoxidase (MPO) activity and lipid peroxidation were significantly reduced in iNOS-KO mice in comparison with iNOSWT mice. Immunohistochemical analysis for nitrotyrosine revealed positive staining in lungs from carrageenan-treated iNOS-WT mice. Lung tissue sections from carrageenan-treated iNOS-WT mice showed positive staining for poly adenosine diphosphate (ADP)-ribose synthetase that was mainly localized in alveolar macrophages and in airway epithelial cells. The intensity and degree of staining for nitrotyrosine and poly-ADP-ribose synthetase were markedly reduced in tissue sections from carrageenan-treated iNOS-KO mice. The inflamed lungs of iNOS-KO mice also showed an improved histologic status. Furthermore, a significant reduction in the suppression of energy status, in DNA strand breakage, and in decreased cellular levels of nicotinamide adenine dinucleotide (NAD(+)) was observed ex vivo in macrophages harvested from the pleural cavity of iNOS-KO mice subjected to carrageenan-induced pleurisy. Taken together, our results clearly show that iNOS plays an important role in the acute inflammatory response.

The intraspinal release of prostaglandin E 2 in a model of acute arthritis is accompanied by an up-regulation of cyclo-oxygenase-2 in the spinal cord

In anaesthetized rats, the intraspinal release of immunoreactive prostaglandin E 2 was measured using antibody microprobes. We addressed the question of whether the release of immunoreactive prostaglandin E 2 is altered during development of acute inflammation in the knee evoked by intra-articular injections of kaolin and carrageenan. We also examined cyclo-oxygenase-1 and cyclo-oxygenase-2 protein levels in the spinal cord during the development of inflammation using the same model of arthritis. Densitometric analysis of microprobes showed that basal release of immunoreactive prostaglandin E 2 in the period 175–310 min after kaolin was slightly higher than in the absence of inflammation. A pronounced enhancement of basal release of immunoreactive prostaglandin E 2 was observed 430–530 min after kaolin. Enhanced levels of immunoreactive prostaglandin E 2 were observed throughout the dorsal and ventral horns. Release of immunoreactive prostaglandin E 2 was not altered further by the application of innocuous and noxious pressure onto the inflamed knee. Western blot analysis revealed that cyclo-oxygenase-2 but not cyclo-oxygenase-1 protein levels were elevated in the spinal cords of animals with inflammation compared to normal animals. This effect was evident as early as 3 h after the induction of arthritis. The maximum elevation of cyclo-oxygenase-2 protein levels (six-fold) was observed 12 h after the induction of arthritis. The results show that there is a tonic release of immunoreactive prostaglandin E 2 from the spinal cord following the induction of arthritis, which is accompanied by enhanced expression of cyclo-oxygenase-2 protein in the spinal cord. We suggest that intraspinal prostaglandins may play a role in inflammation-evoked central sensitizatlon of spinal cord neurons.

Activation and regulation of NFkappaB during acute inflammation.

During the acute inflammatory response, there is induction of a mediator cascade which functions to activate residential macrophages and recruit blood leukocytes to the site of the inflammatory insult. Dysregulation of this process can cause an exaggerated inflammatory response and lead to tissue injury. Recent studies have focused on the transcription factor NFkappaB, which controls the gene expression of many pro-inflammatory mediators. Under normal conditions, NFkappaB is retained in the cytosol by inhibitory proteins of the IkappaB family. In response to an inflammatory insult, IkappaB proteins are degraded and the free NFkappaB complex translocates to the nucleus where it initiates gene transcription. An understanding of the in vivo mechanisms leading to the activation of NFkappaB, and the regulatory mechanisms that exist to limit this activation, may lead to the development of novel new therapeutic options for inflammatory injury. In this review we will discuss the current knowledge of the role of NFkappaB in the development of acute inflammation, as well as the regulatory mechanisms that exist to prevent the activation of NFkappaB and resolve inflammatory tissue injury.

Formalin-induced nociceptive behavior and edema: involvement of multiple peripheral 5-hydroxytryptamine receptor subtypes

The role of 5-hydroxytryptamine and its receptor subtypes in the development of acute inflammation was investigated using the rat paw formalin test as a model for pain (measured by flinching behavior) and edema formation (measured by plethysmometry). The role of endogenously released 5-hydroxytryptamine was assessed using 5-hydroxytryptamine receptor subtype-selective antagonists co-injected with 2.5% formalin, while the receptor subtypes involved in the inflammatory process were further defined by co-injection of 5-hydroxytryptamine or 5-hydroxytryptamine receptor subtype-selective agonists with 0.5% formalin in anticipation of an augmented response. When co-administered with 2.5% formalin, propranolol, tropisetron or GR113808A, but not ketanserin, effectively blocked nociceptive behavior. In the presence of 0.5% formalin, 5-carboxamidotryptamine, 1-( m-chlorophenyl) biguanide or 5-methoxytryptamine, but not (±)-1-4-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, augmented the flinching response. These data suggest involvement of 5-hydroxytryptamine 1, 5-hydroxytryptamine 3 and 5-hydroxytryptamine 4 receptors in peripheral nociception. There may be some dissociation of nociception and edema formation, since no single 5-hydroxytryptamine receptor antagonist inhibited edema formation with 2.5% formalin; however, with 0.5% formalin, edema formation was enhanced by co-administration of 5-hydroxytryptamine, 5-carboxamidotryptamine, (±)-1-4-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane or 5-methoxytryptamine, but not 1-( m-chlorophenyl) biguanide. These data suggest involvement of 5-hydroxytryptamine 1, 5-hydroxytryptamine 2 and possibly 5-hydroxytryptamine 4 receptors in edema formation. These results confirm the involvement of 5-hydroxytryptamine 1 and 5-hydroxytryptamine 3 receptor subtypes in peripheral nociception associated with acute inflammation and further suggest an involvement of the more recently characterized 5-hydroxytryptamine 4 receptor in this process. There appears to be a dissociation in 5-hydroxytryptamine receptors involved in peripheral nociception and edema formation.