RESUMO
The authors pay homage to the three founders of the Brazilian Journal of Medical and Biological Research Profs. Lewis Joel Greene, Sérgio Henrique Ferreira and Eduardo Moacyr Krieger for their vision and commitment to divulge the scientific production of developing countries.
Assuntos
Pesquisa Biomédica/história , Publicações Periódicas como Assunto/história , Brasil , História do Século XX , História do Século XXI , HumanosRESUMO
1. The effect of rapamycin (0.001 to 5 mg kg-1) on the increased leukocyte counts in bronchoalveolar lavage (BAL) fluid and hyperreactivity of isolated bronchial strips to histamine and acetylcholine (ACh) was studied following the intravenous injection of Sephadex beads to guinea-pigs. 2. The intramuscular (i.m.) injection of rapamycin (0.012 to 5 mg kg-1) dose-dependently inhibited the increase in leukocyte counts in BAL fluid. Rapamycin (5 mg kg-1) reduced the numbers of eosinophils neutrophils, macrophages and lymphocytes in BAL fluid by 64, 55, 19 and 50% respectively. In addition, rapamycin (0.012 to 5 mg kg-1) significantly inhibited the Sephadex-induced hyperreactivity of bronchial tissue to both histamine and ACh. 3. At a dose of 0.001 mg kg-1, rapamycin did not significantly reduce leukocyte infiltration or bronchial hyperreactivity. 4. Cyclosporin (5 mg kg-1) significantly reduced both lymphocyte and eosinophil numbers in BAL fluid of Sephadex-injected guinea-pigs whereas dexamethasone (1 mg kg-1) significantly reduced lymphocyte numbers. Neither drug affected the bronchial hyperreactivity to histamine and ACh. 5. It is concluded that the new immunosuppressive drug, rapamycin, is a potent inhibitor of leukocyte migration and bronchial hyperreactivity observed following the intravenous injection of Sephadex beads to guinea-pigs. Rapamycin also appears to be more effective than cyclosporin or dexamethasone in reducing leukocyte counts and bronchial hyperreactivity in this model. 6. Our results suggest that inflammatory mechanisms which are inhibited by rapamycin may be important in the induction of Sephadex-induced hyperreactivity.
Assuntos
Hiper-Reatividade Brônquica/prevenção & controle , Imunossupressores/farmacologia , Leucócitos/efeitos dos fármacos , Polienos/farmacologia , Acetilcolina/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Movimento Celular/efeitos dos fármacos , Ciclosporina/farmacologia , Dexametasona/farmacologia , Dextranos , Feminino , Cobaias , Histamina/farmacologia , Contagem de Leucócitos/efeitos dos fármacos , Masculino , SirolimoRESUMO
The aim of this study was to verify the role played by mononuclear cells in an acute (nonimmune) inflammatory reaction. Mononuclear cells purified from rat peripheral blood were incubated for 1, 2, or 24 h with 100 or 250 microg/ml carrageenin (Cg). The resultant donor supernatant was injected into recipient rats to test its ability to induce hyperalgesia (reduction in threshold for paw pressure) and edema (increase in paw volume). Mononuclear cell supernatants (MnS) induced a significant time- and dose-dependent hyperalgesia and edema in rat paws, which reached a maximal effect at 3 h, lasted for 6 h, and returned to basal levels at 24 h of injection. Prostaglandins and cytokines (interleukin 1, 2, 6, 8, and tumor necrosis factor alpha) accounted for the hyperalgesia induced by MnS, as it was reduced (40 to 90%) by synthesis inhibitors such as indomethacin, dexamethasone, rolipram, and cyclosporin added to the cultures at a microgram dose-range. Edema was dependent on serotonin release in rat paws. These results indicate that mononuclear cells may be important contributors to acute inflammatory reactions, especially under those conditions where pain is an important component.
Assuntos
Edema/etiologia , Hiperalgesia/etiologia , Leucócitos Mononucleares/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Carragenina , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Citocinas/fisiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/metabolismo , Edema/patologia , Feminino , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Cinética , Prostaglandinas/fisiologia , Ratos , Serotonina/fisiologiaRESUMO
The authors pay homage to the three founders of the Brazilian Journal of Medical and Biological Research Profs. Lewis Joel Greene, Sérgio Henrique Ferreira and Eduardo Moacyr Krieger for their vision and commitment to divulge the scientific production of developing countries.