Anti-PD-1 Antibody Administration following Hip Fracture Surgery Reverses Immune Dysfunction and Decreases Susceptibility to Infection

Hao Zhang,Chuying Chen,Jiusheng He,Zhi Liu,Tiansheng Sun,Jianzheng Zhang

doi:10.1155/2019/8492090

Abstract

The aim of this investigation was to assess expression of programmed death-1 (PD-1) and inflammatory status after hip fracture surgery in aged mice and to evaluate the effect of anti-PD-1 antibody intervention. Male C57BL/6 mice aged 22-28 months underwent hip fracture and femoral intramedullary pinning or a sham procedure. Expression of PD-1 was measured on CD4+ and CD8+ T cells. Additionally, the effects of anti-PD-1 antibody on lymphocyte apoptosis, cytokine production, bacterial clearance, and survival were determined. Expression of PD-1 on T cells was upregulated in mice after hip fracture and surgery compared to sham controls. Administration of anti-PD-1 antibody prevented T lymphocyte apoptosis, increased IFN-γ production in splenocytes, and decreased systemic inflammation. Antibody blockade of PD-1 significantly decreased susceptibility to bacteria and improved survival rates of aged mice after hip fracture and surgery followed by the induction of Pseudomonas aeruginosa pneumonia. This study showed that hip fracture and surgical trauma cause significant increases in PD-1 expression in aged mice. Antibody blockade of PD-1 partially reverses T cell apoptosis, decreases the systemic inflammatory response and susceptibility to bacteria, and reduces mortality.

Highlights

As the global population ages, the incidence of hip fractures is increasing
programmed death-1 (PD-1) expression on the surface of splenic CD4+ and CD8+ T cells was found to be significantly increased in mice that underwent intramedullary nailing of hip fractures compared with the sham group 1 and 3 days after surgery (P < 0 05)
Total splenocytes and CD3+ T cell subsets were quantified 48 h after mice that underwent intramedullary nailing of hip fractures or sham surgery were treated with anti-PD-1 antibody, isotype control antibody, or saline

Summary

Introduction

As the global population ages, the incidence of hip fractures is increasing. Between 2002 and 2006, the incidence of hip fractures increased by 58% in women over 50 and by 49% in men over 50 in Beijing [1]. Clinical evidence has shown that infectious complications, such as pulmonary infections, urinary infections, wound infections, and sepsis, are common after hip fracture surgery in elderly patients and seriously affect the prognosis [4, 5]. Severe trauma and surgery can elicit immunosuppression, which significantly inhibits biological processes such as recognition of antigens by immune cells, antigen presentation, T cell activation, and inflammatory cytokine secretion [6]. This decreases the body’s ability to eliminate pathogenic bacteria and increases susceptibility to infection, which can lead to serious complications such as pulmonary infection, sepsis, and multiple organ failure [7].

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