Cytokines Imbalance and their Role in Vitiligo Pathogenesis
Cytokine imbalance has been shown in vitiligo skin [150]. Elevated
serum levels of soluble IL-2 receptor, which correlated with disease
activity in vitiligo patients, have been reported, as have increased
synthesis of IL-6, a cytokine induces ICAM-1 expression on melanocytes
which could facilitate leukocyte–melanocyte interaction, as well as
elevated levels of IL-8, neutrophils, T lymphocytes, and basophils
recruiter [151, 152]. Recently this has been added to by the
revelation of elevation of T helper (Th) 1 (IL-2, interferon (IFN)-γ,
TNF-β), Th2 (IL-4, IL-5, IL-10, IL-13) and Th17 (IL-17, IL-23)-innate
cytokines in the serum of all 44 vitiligo patients examined, with a
higher ratio of Th1/Th2 cytokines [153]. Expression of the
pro-inflammatory cytokine TNF-α is significantly elevated in lesional
and peri-lesional vitiligo patient skin, whereas a variety of
melanogenic mediators such as endothelin-1, stem cell factor, basic
fibroblastic growth factor and granulocyte monocyte-colony stimulating
factor are expressed at lower levels in vitiliginous lesions [154].
Recently it has been shown that melanocyte adhesion is disrupted in
vitiligo skin through increased levels of MMP-9, produced by
keratinocytes in response to IFN-γ and TNF-α, and disturbing E-cadherin
on the pigment cells [155]. Both human patients and a mouse model of
vitiligo, show high levels of IFN-γ, the cytokine required for the
cutaneous recruitment of melanocyte-specific autoreactive CD8+ T
lymphocytes, and of IFN-γ-induced cytokine CXCL10, and its receptor
CXCR3, found on autoreactive CD8+ T cells [71]. Knocking out CXCR3
or blocking CXCL10 action prevents and reverses depigmentation in
vitiligo [76].