Tumor necrosis factor-alpha (TNF-a) and transforming growth factor-beta (TGF-b) in patients with active paracoccidioidomycosis.
THESIS: A. M. R. B. Macedo submitted this dissertation for her Masters in Tropical Diseases at Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil, 1999.
Advisor: Professor Maria Terezinha Serrão Peraçoli
Address to correspondence Address to correspondence A. M. R. B. Macedo Departamento de Doenças Tropicais e Diagnóstico por Imagem, Faculdade de Medicina de Botucatu, UNESP Distrito Rubião Junior, s/n 18618-000, Botucatu, SP, Brasil crisnog@fmb.unesp.br
ABSTRACT: High levels of tumor necrosis factor-alpha (TNF-a) and transforming growth factor-beta (TGF-b) have been associated with the pathogenesis of infectious diseases caused by intracellular microorganisms. This study evaluated the ex vivo production of TNF-a and TGF-b in patients with active paracoccidioidomycosis. Forty patients were divided into two groups by clinical form: 13 with acute form and 27 with chronic. Twenty age-matched healthy individuals were evaluated as controls. Peripheral blood monocytes from patients and healthy controls were cultivated with and without 10 mg/ml Escherichia coli lipopolysaccharide (LPS) for 24 h at 37ºC; TNF-a and TGF-b levels were determined in culture supernatants by ELISA. The results showed that endogenous TNF-a levels in patient monocytes cultivated without stimulus, were significantly higher than those in healthy controls. Cytokine levels were higher in acute form patients than chronic form patients. After monocyte stimulation with LPS, there was a significant TNF-a increase in both patient and control cultures. However, patient monocytes produced significantly lower TNF-a levels in response to LPS than normal subjects, suggesting an impairment in TNF-a capacity production after LPS stimulation. Concentrations of active TGF-b in supernatants from non-stimulated cells were higher in patients than controls; there were no significant differences in monocyte response to LPS between patients and controls. High endogenous TNF-a and TGF-b levels produced by patient monocytes demonstrated the in vivo activation of these cells. Hypo-responsiveness of patient monocytes to TNF-a production after LPS stimulation was demonstrated by negative correlation between TNF-a and TGF-b levels. These results suggest the involvement of TGF-b produced by monocytes in TNF-a production control and immunosuppression in paracoccidioidomycosis.
Key words: TNF-alfa, TGF-beta, paracoccidioidomycosis.
Publication Dates
-
Publication in this collection
09 Dec 2003 -
Date of issue
2003
