RESUMEN
Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9 percent NaCl) or hypertonic saline (HS, 7.5 percent NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor α and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.
Asunto(s)
Animales , Masculino , Ratas , Lesión Pulmonar Aguda/inmunología , Infecciones por Escherichia coli/inmunología , Inflamación/inmunología , Daño por Reperfusión/inmunología , Solución Salina Hipertónica/uso terapéutico , Choque Hemorrágico/tratamiento farmacológico , Enfermedad Aguda , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/microbiología , Citocinas/sangre , Modelos Animales de Enfermedad , Inmunidad Innata , Inflamación/sangre , Inflamación/tratamiento farmacológico , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , ARN Mensajero/sangre , Choque Hemorrágico/inmunología , /sangreRESUMEN
Several studies have shown the relationship between prostaglandins (PGs) and cell proliferation. Some PGs may trigger cell dibision or are involved in this process. This a=study analyzes the effect of PG biosyntheseis inhibitors on tumor growth in vivo and cachexia in Walker 256 tumor-bearing rats. Indomethacin markedly inhibited tumor growth (95.5% while ibuprofen and aspirin reduced tumor growth by 73.9% and 59.4%, respectively. In addition, all drug-treated rats partially recovered body weight and food intake as compared to the saline-treated group. These findings suggest that PG synthesis inhibitors improve cancer cachexia