Pro-inflammatory cytokines such as tumour necrosis factor (TNF) and nitric oxide (NO) are believed to play an important role in the severity of chronic disease. When evaluated in 71 patients who were seropositive for Trypanosoma cruzi and 50 apparently healthy controls, the mean (S.D.) serum concentrations of both TNF [7.65 (1.32) nu. 4.24 (1.53) ng/ml; P<0.001] and NO [114 (40) nu. 74 (21) microM; P<0.0001] were found to be significantly higher in the patients than in the controls. In addition, patients with chronic, symptomatic disease affecting their hearts--eight with dilated cardiomyopathy [8.82 (1.47) ng TNF/ml; 142 (45) microM NO] and 17 others with electrocardiographic alterations [8.37 (1.26) ng TNF/ml; 134 (53) microM NO]--had significantly higher serum concentrations of these cytokines than 34 patients who were in the asymptomatic, indeterminate phase of the disease [6.38 (1.35) ng TNF/ml; 99 (28) microM NO]. In those infected with T. cruzi, it therefore appears that serum concentrations of TNF and NO correlate with disease severity, indicating that these cytokines play some role in the pathogenesis of chronic Chagas disease.
We report here the evaluation of chagasic patients for the presence and/or severity of the disease, antibody to Trypanosoma cruzi, and nitric oxide (NO) serum levels. Serum samples tested by ELISA with autochthonous and commercial antigen revealed that 10% and 7.5% of the individuals were anti-T. cruzi antibody-positive, respectively. Ten of 21 seropositive individuals had no clinical signs, the other 11 cases presented cardiomyopathy and/or mega-gastrointestinal syndromes, and three patients presented a combined form. A statistical difference (P Ͻ 0.001)in antibody titer between asymptomatic and symptomatic patients with autochthonous antigen was detected, and serum NO levels was found to be three times higher in cases than in controls. These results suggest that it is recommended to use a sole source of antigen (autochthonous) for the serodiagnosis of Chagas' disease, and that the pathogenic role of NO in this disease should be evaluated.
In previous studies in animal models, Trypanosoma cruzi-induced oxidative stress and damage have sometimes been controlled by the host's anti-oxidant defence responses. The role of the anti-oxidant defence responses, such as the activities of the anti-oxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD), in protection against inflammation and damage have now been investigated in humans infected with T. cruzi. The subjects were 32 asymptomatic but seropositive individuals with the indeterminate form of Chagas disease, 18 symptomatic and seropositive patients with the chronic disease, and 50 seronegative and apparently healthy controls. The inflammatory process was explored using serum concentrations of tumour necrosis factor (TNF) and NO. The serum concentrations of GPx in the patients in the indeterminate phase of infection were similar to those in the controls but much higher than those in the chronic cases (P=0.001). The serum concentrations of SOD in the patients in the indeterminate phase of infection were not only significantly higher than those in the cases of chronic Chagas disease (P=0.0004) but also significantly higher than those in the controls (P<0.001). The seropositive subjects had significantly higher serum concentrations of TNF and NO than the controls (P<0.01 for each) and the cases of chronic Chagas disease had significantly higher serum concentrations of TNF and NO than the subjects with the indeterminate form of the disease (P<0.01 for each). It therefore appears that the host's anti-oxidant defence responses (at least in terms of elevated concentrations of SOD) may inhibit inflammation during the indeterminate phase of Chagas disease.
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