AI Article Synopsis

  • The study investigates the effects of an anti-IL-17 monoclonal antibody on corneal allograft rejection in mice, aiming to improve graft survival.
  • The results show that the anti-IL-17 treatment significantly prolonged the survival of corneal grafts and reduced inflammation and neovascularization in the treated mice.
  • Additionally, the treatment altered the cytokine production profile, increasing certain Th2 cytokines while reducing pro-inflammatory cytokines, indicating a shift towards a less inflammatory response in the grafts.

Article Abstract

Purpose: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3156778PMC

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