Features of local and systemic production of pro-inflammatory, chemoattractant mediators and vascular growth factors in high-risk corneal transplants

Neroev V.V., Balatskaya N.V., Chentsova E.V., Kulikova I.G., Shamkhalova H.M.

Helmholtz National Medical Research Center of Eye Diseases, Moscow, Russia

Purpose: to study the composition and content of proinflammatory cytokines, chemoattractant mediators, vascular growth factors in blood serum (SB) and lacrimal fluid (LF) in patients with KPHR. Materials and methods. A total of 106 patients with postinflammatory corneal spots and turbid transplant were examined. The control group consisted of 20 practically healthy donors. Cytokines: IL-2, IL-18, MCP-1 / CCL2, MIP-1β / CCL4, RANTES / CCL5, Eotaxin / CCL11, IP-10 / CXCL10, SDF-1α / CXCL12, VEGF-A, VEGF-D, PIGF-1, HGF / SF. Results. The study of the levels of systemic production of immunomodiators in the groups of patients revealed significant changes in the concentrations of MCP-1 / CCL2, RANTES / CCL5, Eotaxin / CCL11, IP-10 / CXCL10, SDF-1α / CXCL12, as well as angiogenic factors VEGF-A and HGF / SF compared to controls. In the group of primary KPHR in the presence of vascularization, an increase in the production of IL-18, RANTES / CCL5, Eotaxin / CCL11 was observed. 1 / CCL2, VEGF-A, PIGF-1 and HGF / SF (p<0.05). Graft vascularization in repeated (2 and higher) corneal transplants (group II) was associated with significant increases in SC IL-2, PIGF-1, and HGF/SF (p<0.05). Analysis of cytokine content in the LF of patients with repeated KPHR and vascularized graft showed a statistically significant increase in IP-10 / CXCL10, MIP-1β / CCL4, SDF-1α / CXCL12, and VEGF-A. A retrospective analysis of the content of cytokines in the SB, depending on the outcomes of keratoplasty, showed a significant increase in the concentration of 7 out of 11 studied cytokines in patients of the KPHR group with various complications in the postoperative period, including those with a developed graft rejection reaction. Conclusions. It has been shown that the formation of vascularized corneal spots is associated with a significant increase in systemic production of IL-18, an increase in the concentration of chemokines with angiogenic activity RANTES / CCL5 and Eotaxin / CCL11 in the blood of patients with KPHR. During vascularization of the graft with repeated KPHR in the SB and LF, a unidirectional increase in the levels of IL-2, MCP-1 / CCL2, growth of VEGF-A and HGF / SF is observed. A factor in the development of graft rejection is the initially high concentrations in the SB of patients with KPHR IL-2, IL-18, chemokines RANTES / CCL5, MIP1β / CCL4, VEGF-A, PLGF, HGF / SF (p<0.05), indicating about the activation of pathological angiogenesis against the background of inflammation and an activated adaptive immune response.