IL-12 and neutralization of endogenous IL-10 revert the in vitro antigen-specific cellular immunosuppression of paracoccidioidomycosis patients

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. © 2002 Elsevier Science Ltd. All rights reserved.

Keywords

Interleukin-10, Interleukin-12, Paracoccidioides brasiliensis, Paracoccidioidomycosis, gamma interferon, glycoprotein, glycoprotein gp 43, interleukin 10, interleukin 12, interleukin 2, neutralizing antibody, unclassified drug, 43 kDa protein, Paracoccidioides, fungal protein, fungus antigen, oligosaccharide, adolescent, adult, aged, cell proliferation, cell stimulation, clinical article, controlled study, cytokine production, cytokine release, human, immune deficiency, immune response, immunomodulation, lymphocyte proliferation, mononuclear cell, priority journal, school child, South American blastomycosis, biosynthesis, child, drug antagonism, drug effect, immunological tolerance, immunology, in vitro study, lymphocyte activation, middle aged, Paracoccidioides, serodiagnosis, Adolescent, Adult, Aged, Antigens, Fungal, Child, Glycoproteins, Human, Immune Tolerance, In Vitro, Interferon Type II, Lymphocyte Activation, Middle Age, Neutralization Tests, Oligosaccharides, Support, Non-U.S. Gov't, Fungal Proteins, Humans, Middle Aged, Candida, Candida albicans