RESUMO
The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles.
Assuntos
Derrame Pleural/imunologia , Pleurodese/efeitos adversos , Talco/farmacologia , Reação de Fase Aguda/imunologia , Animais , Biomarcadores/análise , Biomarcadores/sangue , Injeções , Interleucina-8/análise , Interleucina-8/sangue , Rim , L-Lactato Desidrogenase/análise , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Leucócitos/imunologia , Fígado , Pulmão , Neutrófilos/imunologia , Tamanho da Partícula , Pleurisia/sangue , Pleurisia/imunologia , Pleurodese/métodos , Coelhos , Baço , Talco/análise , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/sangue , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
The aqueous leaves extracts of Passiflora alata (100-300 mg/kg, i.p.) and Passiflora edulis (100-1000 mg/kg, i.p.) possess a significant antiinflammatory activity on carrageenan-induced pleurisy in mice. Treatment with the extracts inhibited leukocyte migration and reduced the formation of exudate. Moreover, a significant inhibition of myeloperoxidase and adenosine-deaminase activities was observed at the doses tested (100 or 250 mg/kg, i.p.). At the same doses, a significant decrease of serum C-reactive protein was observed.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Passiflora , Fitoterapia , Extratos Vegetais/farmacologia , Pleurisia/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Proteína C-Reativa/efeitos dos fármacos , Carragenina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Folhas de Planta , Pleurisia/sangue , Pleurisia/induzido quimicamenteRESUMO
INTRODUCTION: Tacrolimus is an antibiotic macrolide with immunosuppressant properties isolated from Streptomyces tsukubaensis. OBJECTIVES: This study evaluated whether the acute and systemic administration of Tacrolimus significantly interfered in leukocyte migration, exudation, myeloperoxidase and adenosine-deaminase and nitric oxide levels, as well as Interleukin-1 (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels in a mouse model of pleurisy in comparison to those obtained with dexamethasone. MATERIALS AND METHODS: Pleurisy was induced by carrageenan (Cg, 1%), bradykinin (BK, 10 nmol), histamine (HIS, 1 micromol) or substance P (PS, 20 nmol) administered by intrapleural route (ipl.) and the inflammatory parameters (cell migration and exudation) were analyzed 4 h after. In the model of pleurisy induced by carrageenan, other markers in the pleural fluid, such as cytokines (TNFalpha and Il-1beta), nitrite/nitrate (NOx), myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels, were also studied. Dexamethaseone (0.5 mg/kg, i.p., 0.5 h before) was also analyzed in all protocols. RESULTS: In the pleurisy induced by carrageenan, Tacrolimus (1 mg/kg, i.p.) and dexamethasone (0.5 mg/kg, i.p.) administered 0.5 h before caused a significant decrease in leukocytes, neutrophils and exudation (P < 0.01). Under the same conditions, Tacrolimus and dexamethasone did not modify the blood's white or red cells (P > 0.05). Tacrolimus showed a long lasting antiinflammatory effect, inhibiting leukocytes and neutrophils for up to 24 h (P < 0.01), whereas the inhibition of exudation was less marked (up to 2 h) (P < 0.01). These drugs caused a marked reduction in MPO activity, as well as IL-1beta and TNFalpha levels (P < 0.01), but only Tacrolimus inhibited ADA activity (P < 0.01). On the other hand, dexamethasone, but not Tacrolimus, inhibited NOx levels (P < 0.01). In the same conditions, Tacrolimus significantly inhibited cell migration induced by either bradykinin, histamine or substance P (P < 0.05). In a similar manner, dexamethasone inhibited leukocyte influx induced by bradykinin and histamine (P < 0.05). Regarding exudation effects, dexamethasone markedly inhibited this parameter induced by BK, HIS or SP, whereas Tacrolimus only inhibited exudation caused by HIS (P < 0.05). CONCLUSIONS: The results of the present work indicate that Tacrolimus showed important antiinflammatory properties against pleurisy in mice that are different from those caused by dexamethasone. The inhibition of proinflammatory cytokine (TNFalpha, IL-1beta), enzyme (myeloperoxidase, adenosine-deaminase) and mediator (bradykinin, histamine, substance P) release and/or action appears to account for Tacrolimus's actions.
Assuntos
Imunossupressores/administração & dosagem , Pleurisia/prevenção & controle , Tacrolimo/administração & dosagem , Adenosina Desaminase/sangue , Adenosina Desaminase/imunologia , Animais , Antibacterianos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Bradicinina/farmacologia , Bradicinina/toxicidade , Carragenina/farmacologia , Carragenina/toxicidade , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Dexametasona/administração & dosagem , Modelos Animais de Doenças , Histamina/farmacologia , Histamina/toxicidade , Histamínicos/farmacologia , Histamínicos/toxicidade , Humanos , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/prevenção & controle , Interleucina-1/sangue , Interleucina-1/imunologia , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Infiltração de Neutrófilos/imunologia , Óxido Nítrico/sangue , Óxido Nítrico/imunologia , Peroxidase/sangue , Peroxidase/imunologia , Pleurisia/sangue , Pleurisia/induzido quimicamente , Pleurisia/imunologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologia , Vasodilatadores/farmacologia , Vasodilatadores/toxicidadeRESUMO
This study investigated the effect of the platelet-activating factor (PAF) receptor antagonist, PCA 4248, on the rat pleurisy caused by PAF, serotonin, bradykinin, histamine or allergen. The pleurisy was assessed by measuring liquid extravasation and leucocyte infiltration. Oral pretreatment with PCA 4248 (2.5-20 mg/kg) completely inhibited the pleural exudation caused by intrathoracic (i.t.) injection of PAF (1 microgram/cavity) (ED50 = 6.1 mg/kg), partially (42% reduction) the one induced by serotonin (100 micrograms/cavity), but was inactive against histamine (200 micrograms/cavity) or bradykinin (50 micrograms/cavity). PCA 4248 blocked the increase in the number of neutrophils, eosinophils and mononuclear cells observed 6 h after the i.t. injection of PAF, as well as the selective eosinophil accumulation noted 24 h later. In actively sensitized rats, PCA 4248 (20 mg/kg) failed to modify the increase in the total leucocyte counts noted 4 h after ovalbumin (12 micrograms/cavity), but dose dependently inhibited the pleural exudation observed within 1 h and the late eosinophil infiltration noted 24 h post-antigen. These observations led us to suggest that PCA 4248 is a potent PAF antagonist with anti-serotoninergic properties. Its interference with exudation and eosinophil infiltration caused by allergen is consistent with the interpretation that PCA 4248 may be useful in the management of allergic dysfunctions.
Assuntos
Di-Hidropiridinas/farmacologia , Fator de Ativação de Plaquetas/antagonistas & inibidores , Glicoproteínas da Membrana de Plaquetas , Pleurisia/prevenção & controle , Receptores de Superfície Celular/antagonistas & inibidores , Receptores Acoplados a Proteínas G , Alérgenos , Animais , Bradicinina/farmacologia , Edema/induzido quimicamente , Edema/metabolismo , Eosinófilos/efeitos dos fármacos , Exsudatos e Transudatos/citologia , Exsudatos e Transudatos/efeitos dos fármacos , Feminino , Histamina/farmacologia , Hipersensibilidade/metabolismo , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Pleurisia/sangue , Pleurisia/induzido quimicamente , Ratos , Ratos Wistar , Serotonina/farmacologiaRESUMO
Selective platelet-activating factor (PAF) antagonists and autodesensitization to this lipid were used to investigate the role of PAF in antigen-induced pleurisy in the rat. Pleural inflammation was triggered by the intrathoracic (i.t.) injection of ovalbumin (12 micrograms/cavity) into animals actively sensitized 14 days before. Successive daily i.t. injections of PAF (1 microgram/cavity) led to selective autodesensitization, which was apparent after the third injection and maximal after the fifth. The PAF antagonists BN 52021 and WEB 2086 inhibited the late pleural eosinophil accumulation caused by antigen but, as also noted with WEB 2170, failed to modify the early antigen-induced plasma exudation and leukocyte infiltration. In contrast to the antagonists, desensitization to PAF was clearly effective against these early alterations. To further investigate this discrepancy, the antigenic challenge was performed 24 h after a single prestimulation with PAF, when sensitivity to the lipid was still intact. Under this condition, plasma exudation and cellular influx triggered by the antigen were also abrogated, indicating that this protective effect was accounted for by a mechanism other than refractoriness to PAF. Because 24 h after PAF injection only eosinophil counts remained elevated, an alternative eosinophilotactic substance was used to further study the mechanism of PAF versus antigen-induced pleural inflammation. Prior treatment with the peptide Ala-Gly-Ser-Glu (ECF-A, 20 micrograms/cavity) also inhibited the allergic pleurisy, whereas the noneosinophilotactic substances histamine (200 micrograms/cavity) and serotonin (100 micrograms/cavity) were inactive. Furthermore, drugs that share the ability to impair PAF-induced eosinophilia, including azelastine and cetirizine, prevented the inhibitory effect of PAF on the antigen-induced pleurisy. These findings suggest that PAF may account for the late eosinophilia, but not for the acute phase of the rat allergic pleurisy, which is clearly attenuated by PAF or ECF-A pretreatment.