Vascular endothelial growth factor levels in pleural fluid and serum of patients with tuberculous pleural effusions.

We read with great interest the article by Alatas and coworkers (June 2004),1 who showed that serum vascular endothelial growth factor (VEGF) levels were increased in patients with active pulmonary tuberculosis, compared to patients with inactive pulmonary tuberculosis and control subjects. They also showed that serum VEGF levels were statistically different before and after treatment in 10 patients who were observed from diagnosis to the completion of treatment. This study suggests that the levels of VEGF in the serum of patients with pulmonary tuberculosis may serve as a marker of disease activity. We believe that the findings of the study of Alatas et al1 agree with our data regarding the levels of VEGF in patients with tuberculous pleural effusions. We studied VEGF levels in the pleural fluid and serum of 15 patients (9 men and 6 women; mean age, 61.26 17.07 years [ SD]) with tuberculous pleural effusions. Fifteen patients (12 men and 3 women; mean age, 69.23 9.98 years) with transudative pleural effusions due to congestive heart failure (CHF) served as control subjects. Tuberculous pleural effusions were diagnosed by positive culture findings for Mycobacterium tuberculosis or a pleural biopsy specimen showing typical epithelial cell caseating granulomas. All CHF patients had a history of heart failure due to systolic dysfunction (ejection fraction 45%) and presented with bilateral transudative pleural effusions that improved with appropriate treatment with diuretics. The characterization of pleural effusions as transudative or exudative was done according to Light’s criteria.2 VEGF levels were measured with a commercially available enzymeimmunosorbent assay kit (Biosource Europe S.A.; Nivelles; Belgium) according to the protocol of the manufacturer. The levels of VEGF in the pleural fluid of patients with tuberculous pleural effusions were significantly higher compared with the levels of VEGF in the pleural fluid of CHF patients (236.4 156.1 pg/mL vs 59.3 26.98 pg/mL, respectively; p 0.0002). Similar results were observed in the serum of patients with tuberculous effusions and CHF (456.1 295.8 pg/mL vs 217.2 103.8 pg/mL, respectively; p 0.0063). Interestingly, the levels of VEGF in patients with tuberculosis were significantly higher in the serum compared with the pleural fluid (236.4 156.1 pg/mL vs 456.1 295.8 pg/mL, p 0.017) [Fig 1]. The reports of measurement of VEGF levels in tuberculous pleural effusions are scarce.3 The elevated levels of VEGF in the tuberculous effusions of our patients confirm the previously available data. Additionally, the elevated levels in the serum of these patients compared with the CHF control subjects suggest that serum VEGF may be a marker of disease activity in patients with tuberculous pleural effusions, as it is in patients with active parenchymal tuberculosis.1 However, the origin of the VEGF in tuberculous effusions is not clear. In a study by Kraft et al,3 the VEGF levels in malignant pleural effusions were several-fold higher compared to matched serum samples, being suggestive of a significant local release of this cytokine from the tumor within the pleural cavity. Additionally, VEGF has been reported as a major regulator of angiogenesis with an important role in the development of granulomas.5 However, VEGF is a potent inducer of vascular permeability, and may thus represent a significant mediator in pleural fluid formation.6 The significantly higher levels of VEGF in the serum compared to the pleural fluid of our patients are suggestive of the latter role of VEGF, being responsible, at least in part, for the increased vascular permeability that leads to the formation of tuberculous pleural effusions. This is the first study to our knowledge that examines the levels of VEGF both in the pleural fluid and serum of patients with tuberculous pleural effusions, suggesting a possible role of this mediator in the formation of such effusions.