title: Neutralization of mouse interleukin-17 bioactivity inhibits corneal allograft rejection.
abstract: OBJECTIVE
  To investigate the inhibitory effects of anti-mouse interleukin-17 (IL-17) monoclonal antibody (mAb) in high-responder corneal allograft rejection.
  
  
  METHODS
  C57BL/6 or BALB/c mice corneal grafts were grafted onto BALB/c hosts. The neutralizing mouse IL-17 antibody and isotype control were injected intraperitoneally immediately after transplantation for experimental treatment. At appropriate times after treatment, recipient grafts were assessed clinically and histologically, and recipient corneal graft- infiltrating cells were detected by immunohistochemistry and quantified by real-time PCR. The cytokine spleen levels of T helper type 1 (Th1), Th2, and Th17 were analyzed by enzyme-linked immunosorbent assay. Flow cytometric analysis was used to evaluate the frequencies of IL-17-producing Th17 cells.
  
  
  RESULTS
  Neutralization of IL-17 with anti-IL-17 mAb obviously prolonged allograft survival compared to the group that received isotype control. Neovascularizations and inflammatory immune cells in corneal stroma decreased in the allogeneic recipients treated with anti-IL-17 mAb. The mRNA (mRNA) level of graft-infiltrating cells, including neutrophiles, cluster of differentiation 4 (CD4) T cells, and CD8 T cells, decreased dramatically in the IL-17 neutralization group. At days 14 and 42, splenocytes from recipients treated with anti-IL-17 mAb produced significantly less of the pro-inflammatory cytokines interferon-gamma (IFN-γ), IL-12p40, and IL-17 compared to those from control Ig-treated recipients at day 14. However, Th2 cytokine IL-4 and IL-5 production increased, and IL-13 levels were not significantly different among the three groups. IL-6 production was elevated in recipients treated with anti-IL-17 mAb. Anti-IL-17 mAb reduced the percentage of Th17 in CD4+ T cells, but there was no statistical significance between anti-IL-17 mAb and the control group.
  
  
  CONCLUSIONS
  Neutralization of mouse IL-17 bioactivity with anti-IL-17 mAb improves allogeneic corneal graft survival and inhibits corneal allograft rejection to a certain extent by inhibiting production of graft-infiltrating inflammatory cells and decreasing the secretion of pro-inflammatory cytokines.
authors.affiliation: Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: XueDong
authors.initials: X
authors.lastname: Chen
authors.forename: ShiYong
authors.initials: S
authors.lastname: Zhao
authors.forename: XianLing
authors.initials: X
authors.lastname: Tang
authors.forename: HongYan
authors.initials: H
authors.lastname: Ge
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D016039:Corneal Transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D020381:Interleukin-17; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma