Basic fibroblast growth factor and tumour necrosis factor alpha in vitiligo and other hypopigmented disorders: suggestive possible therapeutic targets.

BACKGROUND: In healthy skin, there is a molecular microenvironment that favours the survival of melanocytes and regulates their function. Keratinocytes synthesize and secrete several cytokines that have stimulatory and inhibitory effects on melanocytes. AIM OF THE WORK: This work was conducted to evaluate the expression of basic fibroblast growth factor (bFGF) and tumour necrosis factor alpha (TNF-α) mRNA levels in lesional skin of vitiligo, hypopigmented mycosis fungoides and hypopigmented tinea versicolor. PATIENTS AND METHODS: Forty eight patients (25 vitiligo, 14 hypopigmented mycosis fungoides, 9 hypopigmented tinea versicolor) and 10 healthy controls were included. A 4 mm punch skin biopsy was taken from lesional skin of patients, and the normal skin of controls for quantitative PCR examination of TNF-α and bFGF mRNA. RESULTS: The level of TNF-α mRNA in lesional skin of the three studied disorders was significantly higher than in the control group, while the level of bFGF mRNA was significantly lower in lesional skin of the three diseases than the control skin. A significant inverse correlation was demonstrated between the mRNA levels of the two studied cytokines in vitiligo and hypopigmented MF lesions. CONCLUSION: The study's findings demonstrate that the studied hypopigmented (vitiligo, hypopigmented MF, hypopigmented TV) disorders show similar changes in their cutaneous microenvironment with increased TNF-α and decreased bFGF mRNA expression. This cytokine microenvironment change may be implicated in the pigment loss and hence these cytokines may have future therapeutic implications.

Expression of insulin-like growth factor-I in lesional and non-lesional skin of patients with morphoea.

BACKGROUND: Morphoea (scleroderma) is a chronic disorder characterized by circumscribed sclerotic plaques with the hallmark of increased fibroblast activation and fibrosis. Through its effect on connective tissue cells and immune cells, insulin-like growth factor (IGF)-I has been found to play a role in some autoimmune connective tissue diseases and has been implicated in the pathogenesis of several fibrotic disorders. OBJECTIVES: To evaluate the role of IGF-I in the pathogenesis of morphoea. METHODS: The study was carried out on 15 patients with morphoea and nine healthy controls. Two 5-mm punch skin biopsies were taken from every patient (one from lesional and one from non-lesional skin) and a single biopsy was taken from the normal skin of each control. A 10-mL blood sample was also taken from each patient and control. Quantitative detection of tissue and serum levels of IGF-I was done using an enzyme-linked immunosorbent assay technique. RESULTS: IGF-I in lesional skin was significantly higher than in non-lesional and control skin (P = 0.001 and P = 0.021, respectively). Moreover, a significantly higher level of IGF-I was detected in patient serum when compared with control serum (P < 0.001). A direct significant correlation existed between lesional and non-lesional skin level (r = 0.618, P = 0.014), and between lesional skin level and Rodnan score (r = 0.538, P = 0.039). CONCLUSIONS: Despite the small sample size, this study suggests that IGF-I plays an important role in the pathogenesis of fibrosis, characteristic of morphoea. Studies on a larger number of patients with morphoea as well as on patients with systemic sclerosis are recommended. Furthermore, therapeutic trials using IGF-I antagonist (octreotide) are highly recommended in patients with morphoea.