Paracoccidioidomycosis (PCM) is caused by dimorphic fungi from the
Paracoccidioides brasiliensis
complex.
Previous studies have demonstrated that the severity of disease is associated with a T-helper 2 immune response
characterised by high interleukin (IL)-4 production. In the present study we analysed two polymorphisms in the
IL-4
gene (-590 C/T and intron-3 microsatellite) in 76 patients with PCM and 73 control subjects from an endemic area.
The production of
IL-4 by peripheral blood mononuclear cells after antigen or phytohaemagglutinin stimulation was
determined by ELISA. A significant correlation was observed between the RP2/RP2 intron-3 genotype and infection
with
Paracoccidioides sp. (p = 0.011), whereas the RP1/RP1 genotype was correlated with resistance. No significant
correlation was observed for the
IL-4 promoter polymorphism. Furthermore, the low
IL-4 expression observed in
the control group compared with patients was associated with the RP1/RP1 genotype. These results suggest that
IL-4 polymorphisms might be associated with the ability of the host to control
Paracoccidioides sp. infection. The
relevance of this polymorphism is supported by the observation that patients with disease produce high levels of
IL-4
following mitogen or antigen stimulation. The
IL-4 gene is located in the cytokine cluster region of chromosome 5
where other polymorphisms have also been described.