Il-12 and Neutralization of Endogenous Il-10 Revert the in Vitro Antigen-Specific Cellular Immunosuppression of Paracoccidioidomycosis Patients

Author： Romano C.C. Mendes-Giannini M.J.S. Duarte A.J.S. Benard G.

Publisher： Academic Press

ISSN： 1043-4666

Source： Cytokine, Vol.18, Iss.3, 2002-05, pp. : 149-157

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Abstract

Treatment of patients with paracoccidioidomycosis is still a challenge. Patients present defective lymphoproliferation and IFN-γ responses to the main Paracoccidioides brasiliensis antigen (gp43), which correlates with disease severity. Here, we demonstrated that the patients show also a defective synthesis of interleukin (IL)-12. Therefore, we attempted to revert this immune disfunction by adding IL-12 and neutralizing anti-IL-10 antibody to gp-43-stimulated peripheral blood mononuclear cell cultures. Both treatments increased IFN-γ secretion to levels observed with healthy sensitized individuals, but affected proliferation only modestly. When combined, the treatments further increased IFN-γ synthesis and cell proliferation. The addition of suboptimal concentrations of IL-2 also further increased the IL-12-mediated secretion of IFN-γ. Interestingly, the immune modulation was mostly antigen-specific, since the responses to Candida albicans' antigen were not affected. These results suggest that appropriate immune intervention with cytokines and/or anti-cytokines may help in the treatment of PCM. .