Complex of Natural Cytokines Regulate Post-Burn Regeneration in Cornea

Cytokines form a kind of regulatory net which normal functioning is critical for development of inflammation and regeneration in eye, namely cornea. In connection with this, we studied effects of complex of natural cytokine obtained from pig and comprising activities of IL-1, IL-6, TNF, MIF, TGFbeta1, on post-burn regeneration in rabbit cornea. The cornea burn was induced by 10% NaOH and cytokine complex was locally administered (over month after the burn) to the regeneration site observed as wall-eye. Hystologic analysis and in vitro experiment with mice (F1 hybrids of CBAxC57BL) peritoneal macrophages and human peripheral blood neutrophils were performed to reveal cytokine biological roles. CC augmented post-burn cornea regeneration that is distinctly observed at all regeneration stages and manifested as: (i) action on macrophages at the early regeneration (inhibition of migration, activation of phagocytosis, ROS production, cytokine synthesis and secretion); and (ii) attraction of cornea stromal cells to the regeneration site and enhancement of their main functions (proliferation, fibronectin and collagen synthesis). As a consequence of CC local administration, post-burn regeneration site displayed high plasticity, low scaring and vascularization, being close to those of normal tissue, that finally enabled progression of successful keratoplastics. The data reported below show wide perspectives for administration of natural cytokine complex to treat cornea alterations of various genesis.