Evaluation of IL10 and TGF-beta levels in blood as a biomarker of peri-prosthetic joint infection

The most common area of arthrosis is the hip and knee, where excessive load affects joint surfaces. Although conservative treatment is considered in the first stage of arthrosis treatment, surgical (prosthetic) treatment is planned in the presence of advanced arthrosis. Many complications can be seen during or after arthroplasty surgery. One such complication that can be seen after arthroplasty is periprosthetic joint infection (PJI). PJI is an undesirable situation due to its additional surgical intervention and long-term antibiotic treatment, high cost, and morbidity [1]. Laboratory tests, histopathologic/microbiologic data, and imaging methods should be evaluated together with the clinical diagnosis [2]. A single clinical finding and laboratory test with sufficient sensitivity and specificity routinely used in the diagnosis of PJI has not yet been demonstrated [2-3]. The criteria were defined in the diagnosis of PJI in 2011 by the Musculoskeletal Infection Society (MSIS) [4], and these criteria were modified at the International Consensus Meeting (ICM) in 2013, and they were widely accepted worldwide [5]. These criteria consist of major and minor criteria. The major criteria are as follows: pathogen isolated by culture from two separate tissue/fluid samples from the affected joint or sinus tract communicating with the prosthesis. The minor criteria include elevated erythrocyte sedimentation rate (ESR) (>30 mm/h) or C-reactive protein (CRP) (>10 mg/L); elevated white blood cells (WBC) in synovial fluid (>1100 cells/μL for knees, >3000 cells/μL for hips); elevated synovial polymorphonucleocytes (PMN) (>64% for knees, >80% for hips); pathogen isolation in one culture and intraoperative frozen section of periprosthetic tissue microscopic examination; the presence of >5 PMN per high-power field (hpf) in 5 hpf at x400 magnification [5]. For the diagnosis of PJI, one major criterion or three minor criteria are required [5-6]. PJIs are divided into three as early post-surgical, chronic, and late acute infections (7). Late acute infection is defined as the patient's symptoms starting within the last 3 weeks and 3 months have passed after arthroplasty surgery [7]. In previous studies, it was emphasized that the success rate was high with debridement and insert replacement treatment after the early diagnosis of PJI [3]. If PJI is diagnosed within the first 3 weeks following the development of infection, surgical treatment can be successfully performed without early removal of the prosthesis with early surgical intervention. Early diagnosis of infections that develop after prosthetic surgery is very important because it affects the success of treatment. Today, biomarkers that can be used in early diagnosis of PJI are the subject of research. New clinical methods such as microbiologic culture techniques, molecular methods, and serologic tests used to detect biomarkers from blood and/or joint fluid are used in the diagnosis because milder symptoms are seen in chronic PJI compared with acute infections. The use of biomarkers such as IL-6, CRP, ESR, and alpha defensin is increasing in the diagnosis of PJIs [8,9]. However, accurate and reliable test methods are still required for the early diagnosis of PJIs. IL-10 is a cytokine with an anti-inflammatory effect, suppressing the immune system by inhibiting the activity of Th-1 helper cells, macrophages, and natural killer (NK) cells [10,11]. However, the effects of some cytokines such as IL-10 may not be universally anti-inflammatory. IL-10 also enhances B cell functions and promotes the development of cytotoxic T cells. IL-10 has a regulatory role in immunity against viral, bacterial, fungal, protozoal, and helminth infections [11]. The main sources of IL-10 are helper T cells 2 (Th2), Tr1 cells (a subset of regulatory T cells), Th1, and Th17 cells. However, cytotoxic T cells, monocytes, macrophages, some dendritic cell subgroups (DCs), B cells, and some granulocytes (eosinophils and mast cells) are other important cells that secrete IL-10. IL-10 has effects on the suppression of the immune response by inhibiting the differentiation and maturation of dendritic cells, inhibiting antigen presentation, and inhibiting the production of pro-inflammatory cytokines [IL-1, IL-6, IL-12, and tumor necrosis factor-alpha (TNF-α)]. Moreover, IL-10 is thought to play a regulatory role in B cell activation, NK cell proliferation, and cytokine secretion [12]. TGF-β is an immunomodulatory cytokine, like IL-10. TGF-β is produced by leukocytes, including lymphocytes, macrophages, and dendritic cells, and is a growth factor with many functions that play a role in controlling the differentiation, proliferation, and activation status of these cells. It benefits from the immunosuppressive effect of TGF-β in many chronic diseases [13]. It is important in maintaining pro-inflammatory and anti-inflammatory balance by inhibiting the cellular growth of numerous immune cell precursors. It plays a role in the differentiation of some T cell subgroups, the stimulation of Treg cells, and immune tolerance [14,15]. Also, TGF-β inhibits the release of immunoglobulins from lymphocytes and inhibits the cytotoxicity of mononuclear phagocytes and NK cells [16]. In this study, it was aimed to prospectively investigate the effectiveness of using serum levels of IL-10 and TGF-β for detecting PJIs.