Papel da enzima 5-lipoxigenase na patogênese da artrite séptica experimental

Abstract

Septic arthritis is a joint disease classified as infectious pathology, for instance because it is necessary that a microorganism is capable of penetrating the joint causing the infection. The Staphylococcus aureus is the main cause of septic arthritis, accounting for about 40-60% of cases. Several cell types participate in the immune response to S. aureus in the joint, but neutrophils play an important role in controlling infection due to its arsenal to combat this pathogen. Leukotrienes are lipid mediators with important role in the activation and recruitment of neutrophils. For the biosynthesis of these mediators, the precursor arachidonic acid released from membrane phospholipids and metabolized by the enzyme 5-lipoxygenase (5-LO). This study aimed to evaluate the role of 5-LO in the pathogenesis of experimental septic arthritis. To standardize the model, was performed a response inoculum (104 to 108 CFU of S. aureus i.a) accompanied by a kinetic (1, 7, 14 and 28 days after infection) for evaluation of various inflammatory parameters. The main point of choice is the use of an inoculum of 107 CFU to the analysis conducted after 7 days of infection, when the animals had higher recruitment of inflammatory cells into the cavity, particularly neutrophils, as well as histopathologic score higher and higher loss of proteoglycan . At all times studied was able to recover bacteria from joint and observe increased hypernociception. Mice deficient for the enzyme 5-LO (5-LO-/ -) demonstred less cell recruitment into the joint cavity, together with lower bacterial load, lower histopathological score, lower loss of proteoglycan and hypernociception lower when compared to wild animals. Thus, the absence of the enzyme 5-LO may be considered an important factor in the control of inflammation and bacterial growth in the joint, in that the pharmacological blockade of this enzyme may represent an important therapeutic strategy.