Differential expression of systemic cytokine profiles in Chagasʹ disease is associated with endemicity of Trypanosoma cruzi infections

Chagasʹ disease is a serious public health problem in Paraguay, however the immunoepidemiology of the disease has not been well documented. A preliminary cross-sectional survey was carried out in two villages of the Paraguayan Chaco region and in five villages of the Oriental region to assess the endemicity of Trypanosoma cruzi infections. Thereafter, a subset of individuals (ages ranging from 23 to 65 years) participated in a follow-up study to evaluate clinical and parasitological parameters. Physical examinations and electrocardiograms (ECG) were conducted and blood samples collected for parasite detection and serology. The most frequent ECG abnormalities which were observed among chagasic individuals were left anterior hemifascicular block and right bundle branch block. Thirty-two of these subjects, seropositive and non-parasitemic from the high endemic Chaco (n=16) and low endemic Oriental (n=16) regions, were randomly selected for an analysis of T. cruzi-induced expression of cytokines IL-2, IFN-γ, IL-4 and IL-10 by RT-PCR. The individuals were grouped (n=8) according to the presence or absence of abnormal ECG. In subjects that exhibited abnormal ECG profiles, five of eight (63%) individuals from the high endemic area showed a dominant type 2 (IL-4) response, whereas a comparable number (63%) of subjects from the low endemic area expressed a strong type 1 (IFN-γ) response; the remainder (37%) presented a Th0-type (IFN-γ, IL-4) response. Subjects with normal ECG showed a defined cytokine profile according to endemicity. All subjects from the high endemic region showed a Th0 response, whereas 100% of the individuals from the low endemic area demonstrated a type 1 response. In most chagasic patients regardless of ECG profile and endemicity, IL-2 expression was depressed, while IL-10 mRNA transcripts were consistently elevated. Taken together, these data indicate that chronic human chagasic disease is associated with increased systemic production of type 2 cytokines in response to T. cruzi infection and may be involved in the reciprocal down-regulation of IL-2 production.