Profile of transforming growth factor-beta 1 in patients with dengue haemorrhagic fever

Abstract

The pathogenesis of dengue haemorrhagic fever (DHF) is incompletely understood but it has been suggested that various cytokines may have a role in the process. In this study the profile of the cytokine Transforming Growth Factor-beta 1 (TGF-beta1) was investigated in the sera of 79 patients with various grades of dengue illness and in 21 normal healthy controls. Also, TGF-beta1-specific mRNA was examined in their peripheral blood mononuclear cells (PBMC). The results showed that neither TGF-beta1 protein nor its mRNA were detected in healthy controls. In dengue patients, the TGF-beta1 protein and its mRNA were detected in 96%. However, among the patient groups, the levels of TGF-beta1 were lowest in patients with dengue fever (DF; mean value 315 +/- 95 pg/ml) and were highest in patients with DHF grade IV (mean value 1350 +/- 280 pg/ml; P = < 0. 001). The cytokine appeared during the first four days of illness (304 +/- 90 pg/ml) and gradually increased, reaching peak levels (1050 +/- 215 pg/ml) after the 9th day of the illness. Thus TGF-beta1 in the sera and TGF-beta1-mRNA in the PBMC were present in most of the patients with dengue (96%) but the cytokine levels were highest during the later periods of illness and in patients with DHF grade IV, suggesting a possible role of TGF-beta1 in the pathogenesis of DHF.

Figure 1

Levels of transforming growth factor-β1 (TGF-β1) in cases of dengue. Sera collected from the patients with various grades of the illness were screened for TGF-β1 concentration by sandwich ELISA using commercial kits. The mean value of the data (pg/ml) have been presented. n= total number of the cases in each group.

Figure 2

Amount of TGF-β1 in patients sera (pg/ml) as a function of the stage of dengue illness. n = total number of patients in each group.

Figure 3

Amount of TGF-β1 in patients sera (pg/ml) as a function of the grade and stage of dengue illness. (a) During days 1–4 of the illness; (b) during days 5–8 of illness; (c) from the day 9 onwards of the illness. n = number of patients in each group.

Figure 4

Ethidium bromide-stained agarose gel of PCR products. Detection of the TGF-β1-mRNA (arrow corresponding to 268 bp) amplified from the peripheral blood mononuclear cells (PBMC) of cases of DHF grade IV (Lane 4); grade III (Lane 3); grade II (Lane 8); grade I (Lane 5) and DF (Lanes 6); absence of TGF-β1-mRNA in the PBMC from a normal healthy control (Lane 7); the β-actin (Lane 2) and the TGF-β1 bands were size identified by comparing with the bands of molecular weight marker DNA (Lane 1).