Production of transforming growth factor-beta 1 (TGF-β1) by blood monocytes from patients with different clinical forms of leprosy

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Abstract
In the present study, the concentration of TGF-β1 secreted by adherent cells isolated from human peripheral blood mononuclear cells (PBMC) and either stimulated with PGL-1 or lipopolysaccharide (LPS) or left unstimulated was determined by ELISA. The cells were isolated from untreated patients with different clinical forms of leprosy and healthy individuals. The adherent cells exhibited spontaneous release of TGF-β1 in all clinical forms of leprosy and in healthy individuals; however, lepromatous leprosy/borderline leprosy (LL/BL) patients presenting erythema nodosum leprosum (ENL) displayed significantly higher concentrations of TGF-β1 than either the other patients studied or the controls. These high TGF-β1 levels were consistently observed when LL/BL ENL cells were stimulated with phenolic glycolipid (PGL-1) or LPS, and even in the absence of a stimulus (P < 0·01). The most significant differences in TGF-β1 levels were observed when comparing the results in the presence of PGL-1 from ENL with, in order of significance: tuberculoid leprosy (TT) patients (P < 0·001), LL/BL patients without ENL (P < 0·01), healthy individuals (P < 0·01) and borderline-borderline/borderline-tuberculoid (BB/BT) patients with reversal reaction (RR) (P < 0·01). The BB/BT patients produced equivalent levels of TGF-β1 compared with LL/BL patients without ENL, for all types of stimuli (P > 0·05). In contrast, TT patients produced the lowest levels of TGF-β1 among all the subjects studied (both patients and healthy controls), especially following PGL-1 stimulation (P < 0·001, and P < 0·05, respectively). In conjunction with our previous data regarding TGF-β1 expression in dermal lesions, it appears that TGF-β1 probably plays different roles in leprosy: (i) to mediate a suppressive action locally, associated with the presence of PGL-1, and (ii) to induce proinflammatory effects when secreted systemically by monocytes, thereby acting as a modulatory cytokine in the acute inflammatory reactions of ENL and associated with the Th2 immune response in multibacillary forms of leprosy.