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-gamma 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-gamma secretion to levels observed with healthy sensitized individuals, but affected proliferation only modestly. When combined, the treatments further increased IFN-gamma synthesis and cell proliferation. The addition of suboptimal concentrations of IL-2 also further increased the IL-12-mediated secretion of IFN-gamma. 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.
Romano
Carla C
CC
Laboratório de Alergia e Imunologia Clínica e Experimental LIM 56, Faculdade de Medicina da Universidade de São Paulo, Brazil.
Mendes-Giannini
Maria J S
MJ
Duarte
Alberto J S
AJ
Benard
Gil
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000946:Antigens, Fungal / Q000008:administration & dosage; D002648:Child; D005656:Fungal Proteins; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000037:antagonists & inhibitors*; D018664:Interleukin-12 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008875:Middle Aged; D009500:Neutralization Tests; D009844:Oligosaccharides / Q000008:administration & dosage / Q000276:immunology; D010228:Paracoccidioides / Q000276:immunology; D010229:Paracoccidioidomycosis / Q000276:immunology* / Q000628:therapy*
C103180:43 kDa protein, Paracoccidioides; D000946:Antigens, Fungal; D005656:Fungal Proteins; D006023:Glycoproteins; D009844:Oligosaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma