Skewing of cytokine profiles towards T helper cell type 2 response in visceral leishmaniasis patients unresponsive to sodium antimony gluconate

Thirty-two parasitologically confirmed visceral leishmanisis (VL) patients and 23 healthy, age- and gender-matched controls were recruited between April 2001 and March 2002 and studied for intracellular cytokine production after stimulation in vitro using a Fluorescence Activated Cell Sorter™-based intracellular cytokine assay. The VL patients were given i.m. sodium antimony gluconate at a dose of 20 mg/kg bodyweight daily for 28 d and were grouped as responders (n = 11) or non-responders (no response after 28 d of treatment; n = 21). Clinically, the non-responders had longer duration of illness (P < 0.05), larger spleen size (P < 0.05), and higher parasite load (P < 0.05) than responders. The percentage of T helper (Th) cells producing interferon-γ (IFN-γ) was significantly higher (P < 0.001) in responders than non-responders. Non-responders had higher IFN-γ production than control subjects (P < 0.001). The percentage of Th cells producing interleukin-4 (IL-4) was significantly higher in nonresponders than responders (P = 0.003) as well as in healthy subjects (P < 0.001). The frequency of IL-4 producing cells in responders and control subjects was similar (P = 0.65). The cytokine polarization index, as calculated by the formula loge IFN-γ producing cells/loge IL-4 producing cells, was significantly lower in non-responders compared with both responders and control subjects (P = 0.003 and P < 0.001, respectively). The overall cytokine bias in non-responders was skewed towards a IL-4 dominance or Th2-like response and this was primarily due to induction of IL-4.