IL-6 is a multifunctional cytokine that acts on a wide range of cells.
Several reports have demonstrated its major role as a mediator of
inflammatory and immune responses.
43 The pleiotropic
effects of IL-6 include the stimulation and secretion of
immunoglobulin, induction of neuronal differentiation, and activation
of acute-phase protein synthesized by liver cells. Yan et al.
40 suggested that IL-6 contributes to neovascularization
in pulmonary vessels as a result of prolonged hypoxic exposure. IL-6
expression has been identified during angiogenesis in wound healing and
tumor growth.
44 45 It has been reported that the in vivo
expression of IL-6 accompanies vascularization in female reproductive
tissues.
46 Motro et al.
46 found that maximal
IL-6 mRNA levels coincided with the period of formation of a capillary
network, and no expression was detected once angiogenesis had been
completed. Holzinger et al.
47 indicated that IL-6
was a potent mediator in inducing the proliferation of human umbilical
vein endothelial cells in culture. Moreover, it has been suggested that
IL-6 may be involved in the progression of vascular tumors induced by
Polyomavirus,
48 and Kaposi’s
sarcoma
49 and may stimulate the migration of vascular
endothelial cells in culture.
50 At least 15 intraocular
angiogenic growth factors are known
51 and the most
extensively studied of these molecules include basic fibroblast growth
factor, VEGF, transforming growth factor-β, TNF-α, growth hormone,
insulin-like growth factor-1, IL-8, integrins, and the
angiopoietins.
52 That IL-6 involvement in angiogenesis is
not limited to hypoxia conditions but also occurs in ovulation, wound
healing, and tumor formation suggests that IL-6 should also be
considered an angiogenic factor. Previous evidence
44 45 46 and our own findings indicate that the level of IL-6 in the eye is
highly correlated with the initiation and formation of new vessels.