Pleurisy Induction Research Articles

Toxicological analysis and efficacy of 2-phenylchromone on mycobacteria viability and inflammatory response induced by Mycobacterium bovis

BackgroundStudies have reported that compounds similar to flavone present antimicrobial and anti-inflammatory properties; however these effects are poorly described in the context of mycobacterium infection. Purpose: This study investigated the efficacy of 2-phenylchromone (Flavone) on mycobacteria viability and inflammatory response induced by Mycobacterium bovis, as well as its toxicological potential in in vitro and in vivo models. Methods: In vitro antimycobacterial activity was performed using the resazurin microtiter assay method. In order to investigate the anti-inflammatory action, C57Bl/6 mice were pretreated orally with 2-phenylchromone (1–100 mg/kg) 1 h before the pleurisy induction. The leukocyte migration and cytokine production were evaluated. Acute oral toxicity test, genotoxicity evaluations and splenic phagocytosis assay were also evaluated. ResultsThe minimum inhibitory concentration of 2-phenylchromone in the presence of the Mycobacterium tuberculosis strain was 28.90 µg/mL. In the BCG-induced pleurisy model, the oral treatment with 2-phenylchromone (1, 10, or 100 mg/kg) caused a significant reduction in the tumor necrosis factor (TNF) levels in the pleural exudate, as well as in the total and differential leukocyte counts. The oral treatment with 2-phenylchromone also did not present acute toxicity or genotoxicity in comet assay and micronucleus tests. However, 2-phenylchromone induced an increase of 1.48-times in splenic phagocytosis in the animals. ConclusionOur results showed that 2-phenylchromone did not induced toxicity signs and is effective against Mycobacterium viability and reduced the inflammatory response elicited by mycobacteria.

Systemic Administration of Calea pinnatifida Inhibits Inflammation Induced by Carrageenan in a Murine Model of Pulmonary Neutrophilia.

Objective The aim of this study was to investigate the anti-inflammatory effects of the crude extract (CE), derived fraction, and isolated compounds from Calea pinnatifida leaves in a mouse model of pulmonary neutrophilia. Methods The CE and derived fractions, hexane, ethyl acetate, and methanol, were obtained from C. pinnatifida leaves. The compounds 3,5- and 4,5-di-O-E-caffeoylquinic acids were isolated from the EtOAc fraction using chromatography and were identified using infrared spectroscopic data and nuclear magnetic resonance (1H and 13C NMR). Leukocytes count, protein concentration of the exudate, myeloperoxidase (MPO) and adenosine deaminase (ADA), and nitrate/nitrite (NOx), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β), and interleukin-17A (IL-17A) levels were determined in the pleural fluid leakage after 4 h of pleurisy induction. We also analyzed the effects of isolated compounds on the phosphorylation of both p65 and p38 in the lung tissue. Results The CE, its fractions, and isolated compounds inhibited leukocyte activation, protein concentration of the exudate, and MPO, ADA, NOx, TNF-α, IL-1β, and IL-17A levels. 3,5- and 4,5-di-O-E-caffeoylquinic acids also inhibited phosphorylation of both p65 and p38 (P < 0.05). Conclusion This study demonstrated that C. pinnatifida presents important anti-inflammatory properties by inhibiting activated leukocytes and protein concentration of the exudate. These effects were related to the inhibition of proinflammatory mediators. The dicaffeoylquinic acids may be partially responsible for these anti-inflammatory properties through the inhibition of nuclear transcription factor kappa B and mitogen-activated protein kinase pathways.

The cannabinoid 2 receptor agonist β-caryophyllene modulates the inflammatory reaction induced by Mycobacterium bovis BCG by inhibiting neutrophil migration.

β-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB2) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB2 agonist, GP1a in inflammatory experimental model induced by Mycobacterium bovis (BCG). C57Bl/6 mice were pretreated orally with BCP (0.5-50mg/kg) or intraperitonealy with GP1a (10mg/kg) 1h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB2 agonists on neutrophils function was evaluated in vitro. β-Caryophyllene (50mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-α and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B4 (LTB4), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10µM) impaired chemotaxis toward LTB4 and adhesion to endothelial cells stimulated with TNF-α, and both, BCP and GP1a, impaired LTB4-induced actin polymerization. These results suggest that the CB2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.

Jungia sellowii suppresses the carrageenan-induced inflammatory response in the mouse model of pleurisy.

This study was conducted to explore the anti-inflammatory effect of Jungia sellowii (Asteraceae) using a murine model of pleurisy induced by carrageenan (Cg). This plant is used in southern Brazil to treat inflammatory diseases. J. sellowii leaves were extracted with ethanol/water to obtain the crude extract (CE), which was fractionated with different solvents, yielding n-hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol (BuOH) fractions, and aqueous fraction (Aq). The major compounds succinic acid (SA) and lactic acid (LA) were isolated from Aq fraction, and their structures were determined by (1)H and (13)C NMR. Pleurisy was induced by Cg (Saleh et al. 1996). The leukocytes, exudation, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, metabolites of nitric oxide (NO x ) levels, protein levels and mRNA expression for interleukin 1 beta (IL-1β), tumour necrosis factor alpha (TNF-α), interleukin 17A (IL17A) and inducible of nitric oxide synthase (iNOs), and p65 protein phosphorylation (NF-κB) were analysed 4h after pleurisy induction. Animals pre-treated with CE, BuOH, Aq, SA, or LA inhibited leukocytes, exudation, MPO and ADA activities, NO x , IL-1β, TNF-α, and IL-17A levels, and the mRNA expression for IL-1β, TNF-α, IL-17A, iNOS, and p65 protein phosphorylation (NF-κB) (p<0.05). Our study demonstrated that J. sellowii can protect against inflammation induced by Cg by decreasing the leukocytes and exudation. Its effects are related to the decrease of either proinflammatory cytokines and/or NO x . The isolated compounds SA and LA may play an important role in this anti-inflammatory action by inhibiting all the studied parameters. The anti-inflammatory properties of these compounds are due to the downregulation of NF-κB.

Dual Regulating Effect of Shaoyao-Gangcao-Tang on COX- 2 Expression in Acute and Resolution Phases of Carrageenin-Induced Pleurisy in Rats

Purpose: To investigate the effects and potential mechanisms of Shaoyao-Gangcao-Tang (SGT) on acute and resolution phases of carrageenin-induced pleurisy in rats.Methods: To determine the effects of SGT at 2 h, Sprague-Dawley rats received injection of 0.2 ml of 1 % λ-carrageenin into the pleural cavity after treatment with 4.0, 13.3 and 40.0 g/kg SGT for three days. At 2 h after pleurisy induction, exudate volume, total cell number, prostaglandin E2 (PGE2) production and cyclooxygenase-2 (COX-2) protein expression were measured. To determine the effects at 48 h, the rats were treated with SGT at 24, 36 and 46 h after injection of λ-carrageenin into the pleural cavity, and the exudate volume, total cell number, 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) production and COX-2 protein expression were evaluated.Results: At 2 h after pleurisy induction, 13.3 and 40.0 g/kg SGT significantly decreased exudate volume by 34 (p &lt; 0.05) and b 4 0% (p &lt; 0.01), total cell number by 27 (p &lt; 0.05) and 41 % (p &lt; 0.01), PGE2 production by 17 (p &lt; 0.05) and 35 % (p &lt; 0.01), as well as COX-2 protein expression by 21 (p &lt; 0.01) and 43 % (p &lt; 0.01) compared with control group treated with saline. At 48 h after pleurisy induction, 13.3 and 40 g/kg SGT also significantly decreased exudate volume by 36 (p &lt; 0.05) and 55 % (p &lt; 0.01), as well as total cell number by 31 (p &lt; 0.05) and 43 % (p &lt; 0.01), but markedly increased 15d- PGJ2 production by 26 (p &lt; 0.05) and 51 % (p &lt; 0.01), as well as COX-2 protein expression by 50 (p &lt; 0.01) and 100 % (p &lt; 0.01) compared with control group.Conclusion: The findings suggest that SGT has dual regulating effect in acute and resolution phases of inflammation, involving inhibiting acute inflammation through down-regulation of pro-inflammatory mediators, and promoting inflammatory resolution through up-regulation of pro-resolution mediators.Keywords: Shaoyao-Gangcao-Tang, Cyclooxygenase-2, Prostaglandin E2, 15-Deoxy-Δ12,14-PGJ2, Inflammation

Grape Seed Proanthocyanidin Extract Protects Against Carrageenan-Induced Lung Inflammation in Mice Through Reduction of Pro-inflammatory Markers and Chemokine Expressions

Proanthocyanidins are the most abundant phenolic compounds and have been reported to exert anti-inflammatory actions. The aim of this study was to investigate the effects of grape seed proanthocyanidin extract (GSPE) in a mouse model of carrageenan-induced pleurisy. Following the induction of pleurisy using λ-carrageenan (Cg, 1 %), GSPE (25, 50 and 100 mg/kg) was administered per-oral (p.o.), and the glucocorticoid-induced tumour necrosis factor receptor (GITR), IL-17A expressing cells and other markers, such as cytokines (Th1/Th2 and Th17), were studied. We evaluate the effects of GSPE on the mRNA expression of pro-inflammatory and anti-inflammatory mediators. The results illustrated that the cell numbers of IL-17A and GITR expressing cells and the cytokine levels in Th1/Th17 cells were markedly increased in the Cg-group, whereas the cytokines produced by Th2 cells were significantly decreased in the same group. Treatment with GSPE reversed these effects. Histological examinations revealed anti-inflammatory effects of GSPE.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues

BackgroundDihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. MethodsDHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance (1H and 13C), andmass spectrometry analysiswere used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4h after pleurisy induction. ResultsDHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration andMPOactivity (p<0.05). OnlyDHCsignificantly decreased the exudate concentrations (p<0.01). ConclusionsDHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan.We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

Croton antisyphiliticus Mart. attenuates the inflammatory response to carrageenan-induced pleurisy in mice

The aim of this study was to investigate the anti-inflammatory effect of the crude hydroalcoholic extract (CHE) from the aerial parts of Croton antisyphiliticus, its fractions and isolated compounds derived from it on the mouse model of pleurisy induced by carrageenan. The aerial parts of C. antisyphiliticus were dried, macerated and extracted with ethanol to obtain the CHE, which was fractionated by liquid-liquid extraction using solvents with increasing polarity to obtain hexane (Hex), ethyl acetate (EA) and aqueous (Aq) fractions. Vitexin and quinic acid were isolated from Aq fraction. Capillary electrophoresis analysis, physical characteristics and spectral data produced by infrared (IR), nuclear magnetic resonance ((1)H and (13)C NMR) and mass spectrometry analyses were used to identify and elucidate the structure of the isolated compounds. The experimental model of pleurisy was induced in mice by a single intrapleural injection of carrageenan (1 %). Leukocytes, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitrate/nitrite (NOx), tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) levels were determined in the pleural fluid leakage at 4 h after pleurisy induction. Animals pre-treated with CHE, Hex, EA, Aq, vitexin and quinic acid exhibited decreases in leukocytes, exudate concentrations, MPO and ADA activities and NOx levels (p < 0.05). Also CHE, Hex, EA and vitexin but not quinic acid inhibited TNF-α and IL-17 levels (p < 0.05). C. antisyphiliticus caused anti-inflammatory effect by inhibiting the activated leukocytes, exudate concentrations, NOx, TNF-α, and IL-17 levels. The compounds vitexin and quinic acid may be responsible for this anti-inflammatory action.

PPAR-Gamma Agonist Rosiglitazone Attenuates the Inflammation Caused by Carrageenan in the Mouse Model of Pleurisy

The aim of this study was to investigate the anti-inflammatory efficacy of rosiglitazone (ROSI) in a pleurisy model of carrageenan-induced inflammation. Efficacy was monitored in the mouse pleural cavity by evaluating leukocyte migration, exudate concentration, and myeloperoxidase (MPO) and adenosine deaminase (ADA) activities concomitantly with nitrate/nitrite (NOx), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-17A (IL-17A), and vascular endothelial growth factor-alpha (VEGF-α) levels 4 and 48 h after pleurisy induction. In both phases (4 and 48 h) of pleurisy, ROSI inhibited all the inflammation parameters that were tested (p<0.05). These results provide evidence that ROSI was efficacious in inhibiting pro-inflammatory mediators. These anti-inflammatory effects are assumed to mainly result from the inhibition of products released from activated leukocytes, such as MPO, ADA, NOx, TNF-α, IL-1β, IL-17A, and VEGF-α.

Lotus corniculatus Regulates the Inflammation Induced by Bradykinin in a Murine Model of Pleurisy

This study evaluated the anti-inflammatory efficacy of the crude extract (CE), the fractions derived from hexane (HEX), ethyl acetate (AcOEt), n-butanol (BuOH), and aqueous (Aq) and isolated compounds (oleanolic acid or kaempferitrin) obtained from the aerial parts of Lotus corniculatus var. São Gabriel in mice with bradykinin-induced pleurisy. Swiss mice were used for the In Vivo experiments. Inflammatory parameters [leukocytes; exudate concentrations; myeloperoxidase and adenosine-deaminase activities, and nitric oxide and interleukin-17 levels] were evaluated 4 h after pleurisy induction. The crude extract of Lotus corniculatus, its derived fractions, and isolated compounds inhibited leukocytes and the exudate. This inhibitory effect was associated with decreased of myeloperoxidase and adenosine-deaminase activities, nitric oxide products, and IL-17A levels. Lotus corniculatus presented important anti-inflammatory action by inhibiting leukocyte influx and exudate concentrations. This effect was directly related to the inhibition of nitric oxide and interleukinin17 levels. Oleanolic acid and kaempferitrin can account for these anti-inflammatory effects.

Evidence of anti-inflammatory effects of Pioglitazone in the murine pleurisy model induced by carrageenan

Several studies have shown that the anti-inflammatory effect of Pioglitazone extends beyond the cardiovascular system. This study examines the anti-inflammatory effect of Pioglitazone in comparison to reference drugs (Dexamethasone and Indomethacin) in the mouse model of pleurisy induced by carrageenan which is characterized by two distinct phases (4 and 48 h) of inflammation. Pioglitazone (20 and 50 mg/kg, i.p., 0.5 h before pleurisy) inhibited both neutrophil (4 h) and mononuclears (48 h) influxes ( P < 0.01), but not exudation ( P > 0.05). While one dose of Pioglitazone was effective in inhibiting inflammation at 4 h, additional doses (10 or 20 mg/kg, i.p., 0.5 h before pleurisy induction followed by either a second dose at 24 h after the first one or two further doses at 12 h of time interval after the first one) were necessary to elicit inhibition of the second (48 h) inflammation phase. These effects were associated with a marked decrease in adenosine-deaminase (ADA) activity, tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β) levels ( P < 0.01). Myeloperoxidade (MPO) activity was inhibited only at 4 h ( P < 0.05). By contrast, reference drugs were able to inhibit all the studied inflammatory parameters ( P < 0.05). These results demonstrated an interesting anti-inflammatory property of this thiazolidinedione class and strengthen prior evidence that PPAR pathways constitute another important route of inflammatory process inhibition of this pleurisy model.

Anti-Inflammatory Action of a Phosphatidylcholine, Phosphatidylethanolamine and N-Acylphosphatidylethanolamine-Enriched Diet in Carrageenan-Induced Pleurisy

Background/Aims: Phosphatidylcholine (PC)-derived choline exhibits anti-inflammatory properties in stress conditions. Phosphatidylethanolamine (PE) and N-acylphosphatidylethanolamines (NAPEs) are endogenous bioactive phospholipids linked to the PC and endocannabinoid metabolisms. We hypothesized that an increased dietary input of PC, PE and NAPE may interfere with leukocyte reactions and thus decreases the inflammatory activation. Methods: CFLP mice were fed with a control diet or with a diet supplemented with 1% PC, 0.4% PE and 0.1% NAPE for 7 days before the induction of pleurisy with carrageenan. Pleural leukocyte migration, pulmonary mast cell degranulation (Alcian blue-safranin O staining), and the activities of inducible nitric oxide synthase, xanthine oxidoreductase and myeloperoxidase were determined in lung tissue biopsies. Results: The carrageenan-induced inflammatory response was characterized by pulmonary leukocyte infiltration, mast cell degranulation and significantly increased inducible nitric oxide synthase and xanthine oxidoreductase activities (by 82 and 60%, respectively). Treatment of mice with acetylsalicylic acid or with dietary PC + PE + NAPE supplementation significantly decreased the leukocyte reaction, and suppressed the activity of the pulmonary proinflammatory enzymes. Conclusion: This study confirms a potential for dietary PC + PE + NAPE supplementation to influence events crucial for the remission of acute inflammation. PC + PE + NAPE administration could possibly be a novel preventive or pharmacotherapeutic option in inflammatory pathologies.

Cyclosporin A inhibits CD11a/CD18 adhesion molecules due to inhibition of TNF-α and IL-1β levels in the mouse model of pleurisy induced by carrageenan

The mouse model of pleurisy induced by carrageenan is characterized by a significant enhancement of cell migration due to neutrophils, 4 h after pleurisy induction. Forty-eight hours after pleurisy induction, a significant increase in cell migration due to mononuclear cells occurs. Recently, studies in our laboratory have demonstrated that cyclosporine A (CsA) inhibits leukocyte migration in the pleural cavity and lungs in the mouse model of pleurisy induced by carrageenan. In the present work we evaluated whether CsA was able to downregulate CD11a/CD18 adhesion molecule in the lungs, as well as TNF-α and IL-1β levels in the fluid leakage of the pleural cavity in this model. Our results showed that CsA significantly decreased CD11a/CD18 in the lungs, as well as TNF-α and IL-1β levels in the fluid leakage of the pleural cavity 4 h and 48 h after pleurisy induction. It is our hypothesis that the inhibitory effect elicited by CsA upon these adhesion molecules may be also be attributed to the downregulation of TNF-α and IL-1β cytokines.

Mechanisms of T-Lymphocyte Accumulation during Experimental Pleural Infection Induced byMycobacterium bovisBCG

Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by accumulation of fluid and inflammatory cells in the pleural space. Here, we investigated the mechanisms of T-lymphocyte accumulation in the pleural space by using a murine model of pleurisy induced by Mycobacterium bovis BCG. Intrathoracic (i.t.) injection of BCG (4.5 x 10(5) bacteria/cavity) induced accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy. Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood mononuclear cells to infected mice showed that T lymphocytes migrated into the pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW), but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1 BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and gamma interferon (IFN-gamma). Accordingly, in vivo IL-2 or IFN-gamma neutralization abolished T-lymphocyte accumulation 7 days after pleurisy induction. Our results demonstrate that pleural infection induced by BCG leads to T-lymphocyte accumulation in two waves. The acute phase depends on selectin-mediated migration, while the second wave of T-lymphocyte accumulation seems to depend on a local proliferation induced by cytokines produced in situ.

Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation

Prostanoid production depends on the activity of two cyclooxygenase (COX) isoforms. It is appreciated that COX-1 plays a role in physiological processes, whereas COX-2 acts in pathological conditions. However their roles, particularly roles of COX-1, have not yet been fully established in inflammation. Here, we examined the effects of COX inhibitors, having differential isoform selectivity, on the late phase of rat carrageenin-induced pleurisy to elucidate the role of COX-2 expressed in the draining lymph nodes and found substantial contribution of COX-1-product(s). Protein and mRNA of COX-2 were detectable with Western blotting analysis and reverse-transcription polymerase chain reaction (RT-PCR) analysis in parathymic lymph nodes, peaking at 48 h after induction of pleurisy. Microsomal prostaglandin E synthase (mPGES)-1 was detectable by immunohistochemical analysis in cells with dendritic processes, a morphological characteristic similar to that of COX-2 expressing cells. Although aspirin, indomethacin and a COX-1 inhibitor, ketorolac, significantly decreased the volume of pleural exudate, they did not affect the levels of COX-2 and mPGES-1 in the lymph node 24 h after induction of pleurisy. In contrast, COX-2 inhibitors, nimesulide and NS-398, had no effect on the exudate volume, but they increased the number of COX-2- and mPGES-1-expressing cells and extension of their dendritic processes with significant increase in the COX-2 level, which were antagonised by ketorolac. These results suggest that COX-2-expressing cells may negatively self-regulate their functions by producing PGE 2 via mPGES-1: migration into the draining lymph node and their differentiation. Moreover, COX-1- and COX-2-derived prostanoids may play differential or sometimes antagonistic roles in the late phase of acute inflammation.

Ginkgolide B stimulates signaling events in neutrophils and primes defense activities

Ginkgolide B (GKB) is a bioactive component of the standardized extract from the leaves of the Ginkgo biloba tree (EGb 761), which is used in Chinese and in occidental medicine. GKB is known as a platelet-activating factor receptor antagonist. Here, we provide evidence that GKB per se (0.25–5 μM) stimulated tyrosine phosphorylation of proteins, phospholipase D activation, calcium transients, and activation of p38 but not p44/42 Map kinases in human polymorphonuclear leukocytes (PMN). These stimulatory effects remained relatively weak and primed PMN for subsequent stimulation of respiratory burst (RB) or directed locomotion by the chemoattractant fMet-Leu-Phe (fMLP) or complement-derived factor C5a. A similar RB priming was observed with rat exudate PMN after in vivo administration of EGb 761 (25 and 50 mg/kg) to rats before pleurisy induction. Thus, GKB primarily induces activation of intracellular signaling events and has the potential to prime cellular functions such as PMN defense activities.

Spontaneous Effects of Low-Level Laser Therapy (650 nm) in Acute Inflammatory Mouse Pleurisy Induced by Carrageenan

Our aim was to investigate the effect of low-level laser therapy (LLLT), 650-nm wavelength, on acute inflammatory pleurisy. There is only scattered evidence of anti-inflammatory effects from LLLT and dosage characteristics, and the effect on pleurisy inflammation has yet to be investigated. A classical experimental model of pleurisy was used in a sample of 40 Balb male mice, randomly divided into five groups. Inflammation was induced by carrageenan (0.5 mg/cavity) administered by intrathoracic injections. Four groups received the inflammatory agent, and one received injections of sterile saline solution. At 1, 2, and 3 h after injections, LLLT irradiation was performed, with the same power (2.5 mW), but different irradiation times. The energy densities at each of the three treatment sessions were 0 J/cm(2) (placebo), 3 J/cm(2), 7.5 J/cm(2), and 15 J/cm(2), respectively. Total and differential cell analysis at 4 h after induction of pleurisy showed a significant reduction of inflammatory cell migration for all groups treated with active laser. However, at 4 h after injection, the most significant (p < 0.001) reduction of leukocyte cell migration was seen in the 7.5 J/cm(2) group, at 2.7 (95% CI: 2.5-2.9) x 10(6), versus 7.9 (95% CI: 6.7-9.1) x 10(6) in the placebo control group. The greatest reduction of inflammatory cells was registered for neutrophils. LLLT administered at 1-3 h after the induction of inflammatory pleurisy significantly reduces the inflammatory cell migration measured. Under these conditions and at 2.5 mW, 7.5 J/cm(2) was more effective than 3 J/cm(2) and 15 J/cm(2).

Additional evidence of acute anti-inflammatory effects of cyclosporin A in a murine model of pleurisy

Introduction: It is well known that cyclosporin A (CsA) exhibits important anti-inflammatory effects, besides its immunosuppressive activity. However, the mechanisms by which CsA exerts these effects remain unclear. Objective: This study evaluated whether the acute administration of CsA significantly interfered in leukocyte migration, exudation, myeloperoxidase (MPO) and adenosine-deaminase activities and nitrate/nitrite levels, in a mouse model of pleurisy. Materials and Methods: Pleurisy was induced by carrageenan (1%) treatment and the parameters were analyzed 4 and 48 h after. Groups of animals were previously treated with different doses of CsA and compared with non-treated groups. Results: CsA (0.1–5 mg/kg, intraperitoneal, 1 h before pleurisy induction) inhibited neutrophil migration ( P<0.05), but not the exudation that occurred 4 h after pleurisy induction. At this time, CsA (1 mg/kg, 1 h before) also decreased nitrate/nitrite levels and MPO activity ( P<0.01). CsA (2 mg/kg, 0.5 h before) was also effective in decreasing mononuclear influx, exudation and nitrate/nitrite levels 48 h after onset of inflammation. Conclusions: These results indicate that the acute administration of CsA is able to reduce the two leukocyte populations that occur both at 4 and 48 h after pleurisy induction, late exudation (48 h), MPO activity (4 h) and nitrate/nitrite levels (4 and 48 h). Taken together, these findings indicate that CsA has acute anti-inflammatory effects in immunocompetent animals.

Additional evidence of acute anti-inflammatory effects of cyclosporin A in a murine model of pleurisy

Introduction: It is well known that cyclosporin A (CsA) exhibits important anti-inflammatory effects, besides its immunosuppressive activity. However, the mechanisms by which CsA exerts these effects remain unclear. Objective: This study evaluated whether the acute administration of CsA significantly interfered in leukocyte migration, exudation, myeloperoxidase (MPO) and adenosine-deaminase activities and nitrate/nitrite levels, in a mouse model of pleurisy. Materials and Methods: Pleurisy was induced by carrageenan (1%) treatment and the parameters were analyzed 4 and 48 h after. Groups of animals were previously treated with different doses of CsA and compared with non-treated groups. Results: CsA (0.1–5 mg/kg, intraperitoneal, 1 h before pleurisy induction) inhibited neutrophil migration ( P <0.05), but not the exudation that occurred 4 h after pleurisy induction. At this time, CsA (1 mg/kg, 1 h before) also decreased nitrate/nitrite levels and MPO activity ( P <0.01). CsA (2 mg/kg, 0.5 h before) was also effective in decreasing mononuclear influx, exudation and nitrate/nitrite levels 48 h after onset of inflammation. Conclusions: These results indicate that the acute administration of CsA is able to reduce the two leukocyte populations that occur both at 4 and 48 h after pleurisy induction, late exudation (48 h), MPO activity (4 h) and nitrate/nitrite levels (4 and 48 h). Taken together, these findings indicate that CsA has acute anti-inflammatory effects in immunocompetent animals.

Coordinate cytokine gene expression in vivo following induction of tuberculous pleurisy in guinea pigs.

Tuberculous pleurisy is a severe inflammatory response induced by Mycobacterium tuberculosis organisms that have escaped from lung granulomata into the pleural space during pulmonary infection. We have used the guinea pig model of tuberculous pleurisy to examine several aspects of the immune response to this antigen-specific inflammatory event. Pleurisy was induced by injection of heat-killed M. tuberculosis H37Rv directly into the pleural space of guinea pigs previously vaccinated with M. bovis BCG. Four animals were euthanized each day over a period of 9 days. Fluid in the pleural cavity was analyzed for transforming growth factor beta 1 (TGF-beta 1) and total interferon (IFN) protein levels. In addition, RNA was obtained from pleural cells and examined for TGF-beta 1, tumor necrosis factor alpha (TNF-alpha), IFN-gamma, and interleukin-8 (IL-8) expression by real-time PCR. Finally, pleural cells were examined for the ability to proliferate in response to concanavalin A and purified protein derivative (PPD) in vitro. In the pleural fluid, TGF-beta 1 protein concentrations increased over the course of the inflammatory response while IFN protein levels were not significantly altered. Expression of TGF-beta 1 mRNA peaked on days 3 and 4, and IFN-gamma mRNA expression peaked on day 3 and then returned to background levels. TNF-alpha mRNA expression was highest on days 2 to 4, and IL-8 mRNA levels remained elevated between days 2 and 5, peaking on day 3 before returning to background levels. PPD-induced proliferative responses were evident by day 3 and remained present throughout the study. Analysis of cytokine expression during tuberculous pleurisy may lead to a better understanding of the self-healing nature of this manifestation of tuberculosis.