Circulating T Helper 1 (Th1) Cell- and Th2 Cell-Associated Cytokines in Indian Patients with Visceral Leishmaniasis

Shyam Sundar Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Corixa Corporation, Department of Medicine, Cornell University Medical College, Varanasi, India

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Steven G. Reed Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Corixa Corporation, Department of Medicine, Cornell University Medical College, Varanasi, India

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Sashi Sharma Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Corixa Corporation, Department of Medicine, Cornell University Medical College, Varanasi, India

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Amit Mehrotra Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Corixa Corporation, Department of Medicine, Cornell University Medical College, Varanasi, India

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Henry W. Murray Kala-Azar Medical Research Center, Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Corixa Corporation, Department of Medicine, Cornell University Medical College, Varanasi, India

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Sera from 61 Indian patients with visceral leishmaniasis caused by infection with Leishmania donovani were tested for the presence of T helper 1 (Th1) cell-(interferon-γ [IFN-γ]) and Th2 cell-associated cytokines (interleukin-4 [IL-4] and IL-10). The IFN-γ activity was detected in 53%, IL-4 in 84%, and IL-10 in 56% of patient samples. Sera from 10 healthy Indian controls showed detectable IFN-γ in 90%, IL-4 in 10%, and IL-10 in 20%; corresponding percentages for sera from eight healthy American controls were 100%, 12%, and 0%, respectively. Quantitative data for the 61 patients compared with the 10 Indian controls indicated comparable mean levels of IFN-γ, but three- and 13-fold increases in IL-10 and IL-4, respectively. Undetectable IFN-γ activity, observed in 47% of patients, was associated with the presence IL-4 alone or in combination with IL-10 but not with IL-10 alone. In patients who had failed prior therapy (n = 29) compared with previously untreated patients (n = 32), IFN-γ levels were 67% lower and IL-4 levels were two-fold higher; IL-10 activity was comparable. These results using peripheral blood support the presence of a suppressive Th2 cell-associated immune response in symptomatic Indian kala-azar and point to a possible role for IL-4.

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