Abstract
Little information is available on the functional activity of leukocytes after arthroplasty or the expansion of populations with immune suppressive properties during the acute post-operative period. Synovial fluid and matched pre- and post-surgical blood samples were collected from total hip and knee arthroplasty patients (THA and TKA, respectively) to examine the impact of surgery on peripheral blood leukocyte frequency, bactericidal activity, and inflammatory mediator expression. For spinal surgeries, inflammatory mediator production by peripheral blood mononuclear cells (PBMCs) pre- and post-surgery was examined. An expansion of immune suppressive granulocytic myeloid-derived suppressor cells (G-MDSCs) was observed following arthroplasty, which correlated with significantly increased serum interleukin-10 (IL-10) levels. Analysis of synovial fluid from THA and TKAs revealed reduced granulocyte colony-stimulating factor (G-CSF) and soluble CD40 ligand (sCD40L) and increased interleukin-6 (IL-6), monocyte chemoattractant protein 2 (CCL2) and Fms-like tyrosine kinase 3 ligand (Flt-3L) compared to pre- and post-surgical serum. For the spinal surgery cohort, stimulation of PBMCs isolated post-surgery with bacterial antigens produced significantly less pro-inflammatory (IL-1α, IL-1β, interleukin-1 receptor antagonist (IL-1RA), IL-12p40, growth-related oncogene-α/GRO-α (CXCL1) and 6Ckine (CCL21)) and more anti-inflammatory/tissue repair mediators (IL-10, G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF)) compared to PBMCs recovered before surgery. The observed bias towards systemic anti-inflammatory changes without concomitant increases in pro-inflammatory responses may influence susceptibility to infection following orthopaedic surgery in the context of underlying co-morbidities or risk factors.
Highlights
Joint arthroplasty is the most common orthopaedic procedure in the United States [1]
We have shown that a heterogeneous subset of immature monocytes and granulocytes, called myeloid-derived suppressor cells (MDSCs), are recruited to tissues during prosthetic joint infection (PJI), where they exert anti-inflammatory effects [11,12,13]
The first purpose of this study was to determine if orthopaedic procedures caused the expansion of MDSCs that possess immune inhibitory activity and whether this translated into differences in leukocyte effector function
Summary
Joint arthroplasty is the most common orthopaedic procedure in the United States [1]. Total knee and hip arthroplasties (TKA and THA, respectively) alleviate pain and improve mobility and quality-of-life. Over 1 million procedures are performed in the United States each year [2] and by 2030, it is projected that the demand for primary and revision TKA and THA will total over 4 million cases [3,4]. This increase is driven by an aging population, higher rates of diagnosis and treatment of advanced arthritis, and expansion of surgical treatment to younger, more active patients [2]. Several studies have characterized this post-operative inflammatory reaction by the heightened production of several proinflammatory mediators, including interleukin (IL)-1β and tumor necrosis factor α (TNF-α), which can induce the release of other cytokines, such as IL-6 that has been correlated with post-operative complications after arthroplasty [7]
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