Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with human paracoccidioidomycosis.
Patients with paracoccidioidomycosis (PCM) display a certain degree of immunecompromise characterized by lymphocyte hyporesponsiveness to the main Paracoccidioides brasiliensis antigen (gp43). To determine whether cytokines are involved in this state, we evaluated the secretion of IL-2, IL-10 and IFN-gamma by peripheral blood mononuclear cells (PBMC) from patients with the acute (AF) and chronic (CF) forms of PCM and from healthy, P. brasiliensis-sensitized subjects. gp43-stimulated PBMC from healthy subjects produced substantial amounts of IL-2, IFN-gamma and IL-10, whereas PBMC from AF and CF patients produced low levels of IL-2 and IFN-gamma but substantial amounts of IL-10. Phytohaemagglutinin-induced cytokine secretion was comparable among AF and CF patients and healthy subjects, suggesting integrity of non-specific cellular immune mechanisms in PCM. gp43-pulsed adherent cells, but not non-adherent cells, were the main source of IL-10. Moreover, IL-2 and IFN-gamma secretion correlated inversely with the amount of specific antibodies produced by patients and healthy subjects. Our results suggest that the imbalance in cytokine production of patients with PCM plays a role in the gp43-hyporesponsiveness and the marked (non-protective) antibody production of these patients.
Laboratório de Alergia e Imunologia Clínica e Experimental, LIM-56, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. mahong@usp.br
G
G
Benard
C C
CC
Romano
C R
CR
Cacere
M
M
Juvenale
M J
MJ
Mendes-Giannini
A J
AJ
Duarte
D000293:Adolescent; D000328:Adult; D000946:Antigens, Fungal / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010228:Paracoccidioides / Q000276:immunology; D010229:Paracoccidioidomycosis / Q000276:immunology*
D000946:Antigens, Fungal; D016207:Cytokines; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma