Interleukin (IL)-10 is a potent immunosuppressant of monocyte/macrophage function and may help control the inflammatory response induced by bacterial infection. To analyze whether IL-10 is detectable in plasma of patients with septic shock and to evaluate its relationship with endotoxin (lipopolysaccharide [LPS])-induced and monocyte/macrophage-induced inflammatory response, plasma IL-10, tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-6, IL-8, LPS, and neopterin were studied in 24 patients with septic shock and in 12 critically ill patients. Eighty-three percent of patients with septic shock and 25% of critically ill patients had detectable levels of IL-10 (P < .001). There was a significant correlation between plasma IL-10, neopterin (r = .72), TNF-alpha (r = .76), IL-6 (r = .68), and IL-8 (r = .61) levels in patients with septic shock. Monocyte/macrophage activation leads to massive secretion of IL-10, which, however, seems to be unable to control the increased production of proinflammatory mediators during septic shock.

The plasma levels of endotoxin, tumor necrosis factor- alpha (TNF-alpha), interleukin -1 beta (IL-beta), IL-6, IL-8 and the nitrites and nitrates (NO2-/NO3-) as stable metabolites of nitric oxide (NO) were studied in the plasma of 2 patients with the streptococci toxic shock syndrome (STSS) associated to necrotizing fasciitis. A plasma profile of inflammatory mediators with high cytokine concentrations and NO2-/NO3- were observed with circulating endotoxin not being detected in plasma. The first patient died of fulminant refractory shock while the second survived following subacute evolution. The mediators profile, which was much higher in the first case, coincided with clinical severity. These data suggest that the cytokines and NO may have a role in the physiopathology of STSS and the severity of it is related to the levels of these mediators in the acute phase.

OBJECTIVE:To investigate the relationship between nitric oxide production, endotoxemia, and hemodynamic alterations in human septic shock.DESIGN:Prospective study.SETTING:A 32-bed intensive care unit in a university referral hospital.PATIENTS:Two groups of septic patients with shock (n = 13) or without shock (n = 16) and an additional group of nonseptic patients as control group (n = 25).MEASUREMENTS:Plasma nitrite and nitrate concentrations were measured as an index of nitric oxide generation. Nitrite and nitrate concentrations were correlated with plasma endotoxin and hemodynamic variables.MAIN RESULTS:Increased plasma nitrite and nitrate concentrations were found in patients with septic shock (p < .01). Nitrite and nitrate correlated directly with endotoxin concentration (r2 = .21, p < .05) and cardiac output (r2 = .49, p < .05), and inversely with systolic blood pressure (r2 = .24, p < .01).CONCLUSIONS:This study demonstrated the activation of the L-arginine:nitric oxide pathway in human endotoxemic septic shock, suggesting that nitric oxide may be an important mediator of the hemodynamic disturbances in this pathophysiologic situation.

Sepsis is the most important cause of mortality in the Intensive Care Units. At present, sepsis is understood to be the inflammatory response of the host to infection, rather than a direct effect of microbial aggression. From the clinical standpoint, this inflammatory response is known as systemic inflammatory response syndrome (SIRS). Pathophysiologically, SIRS is characterized by the activation of several groups of cell (monocytes/macrophages, PMNs, and endothelial cells) and by the release of inflammatory mediators (cytokines and others). Tumor necrosis factor (TNF) is the first cytokine released by endotoxin action over monocyte/macrophage. TNF secretion, modulated by interferon gamma (IFN gamma) and interleukin 10 (IL-10), is followed by release of other cytokines such as interleukins (IL) (IL-1, IL-6 and IL-8). These mediators are able to act over hemostasis activating the extrinsic pathway through tissue factor expression. The action of the mediators over endothelial cells induces an increase in plasminogen activator inhibitor type 1 (PAI-1) levels with inhibition of fibrinolysis. Both coagulation activation and fibrinolysis blockade result in fibrin deposit in the microvascular system. The complexity of the mechanisms implicated in systemic inflammatory response make a general rule so difficult to establish, because patient response is highly individualized and it is not possible to know which moment of this dynamic process is being analyzed.

The clinical picture, treatment and evolution of seven patients presenting snake bites are analyzed, Local symptoms were constant, with a spontaneous favorable evolution in 7 to 10 days. The most relevant systemic manifestations were coagulation anomalies which appeared in two patients. Treatment always included local wound care, antitetanic antibiotic and anticoagulant prophilaxis with specific antiophidic serum in five patients.

The clinical picture, treatment and evolution of seven patients presenting snake bites are analyzed. Local symptoms were constant, with a spontaneous favorable evolution in 7 to 10 days. The most relevant systemic manifestations were coagulation anomalies which appeared in two patients. Treatment always included local wound care, antitetanicum antibiotic and anticoagulant prophylaxis with specific antiophidic serum in five patients.