Macrophage Activation by Patients Serum and its Correlation with Sepsis Outcome
Lorenzi, R.1; Andrades, M.1; Ritter, C.1,2; Lopes, T.2; Moreira, J.C.F.1; Dal-Pizzol, F.1,2.
1 Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, UFRGS, RS; 2 Laboratório de Fisiopatologia Experimental, UNESC, SC.
INTRODUCTION: The cytokine secretion by macrophages has been studied to determine patterns of activation of this cells. Generally, two patterns have been found: pro and antiinflammatory. The latter is known as alternative activation. The cytokines (i.e. IL-1b, TNF-a) play an important role in determining which type of activation the macrophages will go through.
OBJECTIVE: This study aimed to determine the relationship between macrophage activation induced by serum from septic patients and the severity and outcome of sepsis.
METHODS: Blood was collected, in the time of diagnosis, from sepsis (Se), severe sepsis (SSe) and septic shock (SSh) patients. Patient's data were collected until hospital discharge. Peritoneal macrophages were harvested from Wistar rats, cultured and activated with patients sera. Control macrophages were activated with serum from healthy volunteers and from coronary artery bypass grafting surgery patients. After an incubation of 6 hours, medium was collected for pro-inflammatory cytokines (IL-1b, TNF-a) and nitric oxide release assay.
RESULTS: SSh patients serum, when compared to Se and SSe serum, induced a decrease in TNF-a and nitric oxide release by macrophages. Serum from SSe patients induced a decreased in the release of IL-1b and TNF-a from macrophages when compared to Se. There was a strong and significant correlation between Multiple Organ Dysfunction Score and IL-1b and TNF-a release. This was also true to the correlation of this cytokines and mortality.
CONCLUSION: Macrophage activation by septic pacients serum differs according to the severity of the disease. This pattern of activation was suggestive to Compensatory Antiinflammatory Response Syndrome (CARS) and it suggests that late stages of the disease are not related to hyperimmune response.
|