ELEVATED IL-10 MESSENGER-RNA EXPRESSION AND DOWN-REGULATION OF TH1-TYPE CYTOKINES IN MICROFILAREMIC INDIVIDUALS WITH WUCHERERIA-BANCROFTI INFECTION

To understand the molecular basis of parasite-specific anergy in human lymphatic filariasis caused by the nematode Wuchereria bancrofti, par asite antigen-dependent cellular proliferation and cytokine gene expre ssion were investigated. By reverse transcriptase polymerase chain rea ction (RT-PCR), the levels of cytokine mRNA were determined in the per ipheral blood mononuclear cells (PBMCs) of different clinical groups o f filariasis patients. This includes individuals with circulating micr ofilariae (MF), patients with chronic lymphatic obstruction (CP), and exposed but uninfected individuals (EN). Those with CP exhibited both a Th2 and a Th1 parasite antigen-driven response. In PBMCs from those with MF, there was a marked downregulation of cellular response to par asite antigens, with lowered expression of Th1-specific cytokines (IFN -gamma and IL-2) and this was paralleled by increased IL-10 expression . The EN individuals had a purely TH1-type pattern with absence of IL- 4 and IL-5 expression. Further, the mRNA expression of the costimulato ry surface marker, CD80 (B7-1), was not associated with either disease status or IL-10 expression. There was a significant negative correlat ion between IL-10 mRNA expression and PBMC proliferation in the MF ind ividuals, thus indicating the possible role of IL-10 in antigen-specif ic hyporesponsiveness.