BACKGROUND: More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status.
METHODS: Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status.
RESULTS: After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI.
CONCLUSIONS: In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.

Platelet-rich plasma (PRP) has been increasingly used in sports medicine owing to its various advantages. The purpose of our project was to standardize the parameters before performing large-scale clinical trials in the near future to precisely evaluate individual PRP quality. To examine the effects of regular exercise on PRP quality, this study focused on young female athletes, who have been relatively less studied. Blood samples were obtained from female college athletes (n = 35) and ordinary healthy adults (n = 30), which were considered as controls, and leukocyte-rich PRP (L-PRP) was prepared manually. Body composition indices were determined using a bathroom weight scale equipped with an impedance meter. Growth factors and cytokines were quantified using ELISA kits. Platelet-derived growth factor-BB (PDGF-BB) and Transforming-growth factors β1 (TGFβ1) levels (per platelet) in L-PRP were significantly lower in female athletes than in controls. In contrast, Interleukin-1β and Interleukin 1 receptor antagonist (IL-1RA) levels (per platelet and L-PRP) in L-PRP were significantly higher in athletes, and this difference was more prominent in IL-1RA. These findings suggest that L-PRP from athletes may facilitate the inflammatory phase of the healing process by regulating the pro-inflammatory and anti-inflammatory balance. These chemical compositions can be adopted as \"must-check\" parameters to characterize individual PRP preparations prior to clinical trials.

Objective: Chronic inflammation is considered as playing an important role in the pathophysiology of atherosclerosis, but the exact contributing inflammatory pathway on stroke is not clear. We aimed to examine the causal association of inflammatory biomarkers, such as interleukin-1 receptor antagonist (IL-1Ra), soluble interleukin-6 receptor (sIL-6R) and C-reactive protein (CRP), with the risk of ischemic stroke and its subtypes.Methods: Two-sample mendelian randomization analyses were performed using IL-1Ra, sIL-6R and CRP related genetic variants as instrumental variables. Summary-level data on ischemic stroke and its subtypes were obtained from the largest GWAS meta-analysis on stroke to date - the Multiancestry Genome-wide Association Study of Stroke (MEGASTROKE) consortium. Associations of IL-1Ra with stroke or its subtypes were estimated using inverse-variance weighted (IVW) method with SNPs rs6743376 and rs1542176 as instruments. Wald ratio method with SNP rs2228145 as the instrument was used for sIL-6R and IVW, MR-Egger, simple and weighted median approaches with 4- or 18-SNPs instruments were used for CRP.Results: Genetically elevated ln(IL-1Ra), ln(sIL-6R) and ln(CRP) levels were not causally associated with ischemic stroke (OR = 1.00, 95% CI: 0.97-1.04, p = 0.80; OR = 0.93, 95% CI: 0.87-0.99, p = 0.03; OR = 1.01, 95% CI: 0.94-1.09, p = 0.78). No significant association was observed between ln(IL-1Ra), ln(sIL-6R) and ln(CRP) level and ischemic stroke subtypes.Conclusions: Our study did not find convincing evidence to support that inflammatory biomarkers like IL-1Ra, sIL-6R and CRP are causally associated with the risk of ischemic stroke or its subtypes.

This study aimed to investigate the association of IL-1RA VNTR and IL-1α 4845G>T polymorphisms with idiopathic male infertility followed by an in silico analysis. In a case-control study, we collected blood samples from 230 infertile and 230 healthy men. Genotyping of IL-1RA VNTR was performed by PCR whereas IL-1α 4845G>T was genotyped by polymerase chain reaction-restriction fragment length polymorphism. An in silico approach was employed for the detection of IL-1RA VNTR and IL-1α 4845G>T effects on some molecular aspects of IL-1RA and IL-1α respectively. The result of our genetic association study for IL-1α 4845G>T revealed that there was a significant association between GT genotype, TT genotype, T allele and idiopathic male infertility. Although there was no significant association between IL-1RA VNTR and male infertility in the overall analysis. However, subgroup analysis revealed that the subjects with VNTR 4R/5R genotype were at a higher risk of oligozoospermia. Furthermore, 4845TT genotype, and 4845T allele were associated with oligozoospermia, asthenozoospermia and nonobstructive azoospermia. Bioinformatics analysis showed that IL-1RA VNTR may affect the splicing pattern of IL-1RA. Moreover, IL-1α 4845G>T has a significant effect on RNA structure and protein function. Based on our findings, both IL-1RA VNTR and IL-1α 4845G>T polymorphisms could be considered as potential biomarkers for screening of susceptible individuals.

This study compared the effects of 12 weeks of high-intensity interval body weight training (HIBWT) with combined training (COMT; aerobic and resistance exercises on body composition, a 6-minute walk test (6MWT; physical performance), insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at high risk of type 2 diabetes mellitus (TDM2).
In this randomized controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated into two groups: HIBWT (n = 8) and COMT (n = 8). The HIBWT group performed a training protocol (length time ~28 min) consisting of ten sets of 60 s of high intensity exercise interspersed by a recovery period of 60 s of low intensity exercise. The COMT group performed a training protocol (length time ~60 min) consisting of a 30 min walk of moderate intensity following by five resistance exercises. All training sessions were performed in the university gym facility three days a week (no consecutive days) for 12 weeks. All outcomes (body composition, muscle function, and IR and inflammatory markers) were assessed at the baseline and at the end of the study.
Both groups increased (P < 0.05) muscle mass index (MMI), 6MWT, and interleukin 1 receptor antagonist and decreased fasting glucose, glycated hemoglobin, Insulin, HOMA-IR, and monocyte chemoattractant protein-1 (trend, P = 0.056). HIBWT effects were indistinguishable (P > 0.05) from the effects of COMT. There was a significant (P < 0.05) interaction of time by the group in muscle strength, indicating that only the COMT increased the muscle strength.
This study suggests that changes in HOMA, IL-1ra, 6MWT, and MMI with HITBW are similar when compared to COMT in PW at high risk of TDM2.
The patients were part of a 12-week training study (ClinicalTrials.gov Identifier: NCT03200639).

Osteoarthritis (OA) is a progressive and degenerative disease, which may result in significant pain and decreased quality of life. Recent updates in our understanding of OA have demonstrated that it is a whole joint disease that has many similarities to an unhealed wound containing inflammatory cytokines. The nSTRIDE Autologous Protein Solution (APS) Kit is a medical device under development for the treatment of OA. The APS Kit processes a patient\'s own blood at the point of care to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors. This study assessed the safety and treatment effects of a single intra-articular injection of APS. Eleven patients were enrolled in this study. Sufficient blood could not be drawn from one patient who was subsequently withdrawn, leaving 10 patients treated. Minor adverse events (AEs) were experienced by seven subjects (63.6%). There was one serious AE (diverticulitis) unrelated to the device or procedure. One subject experienced AEs that were judged \"likely\" to be procedure related (arthralgia/musculoskeletal discomfort) and all resolved within 6 days of injection. All other AEs were unrelated to the device or procedure. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores improved significantly over time (ANOVA, p < 0.0001, 12.0 ± 1.2 preinjection, 3.3 ± 2.9 one year postinjection, and 72.5% WOMAC pain improvement). There was significant positive correlation between white blood cell concentration in APS and improvement in WOMAC pain scores.

Current osteoarthritis (OA) research searches for treatments that modify the course of disease progression. Autologous Protein Solution (APS) is derived from whole blood and is a unique autologous therapy that contains high concentrations of white blood cells, platelets, and concentrated plasma, providing cytokines that can target the underlying mechanisms of disease progression. The APS Kit is currently under investigation for clinical use in the USA (NCT02262364). The aim of this study was to determine if APS has disease-modifying properties in the well-characterized rat meniscal tear-induced model of OA. Thirty male athymic rats underwent surgery to induce OA by a complete tear of the medial meniscus of the right knee. Seven days later, rats were administered 50 μl intra-articular (IA) APS from a human donor or phosphate buffered saline (PBS) control. Rats were euthanized 3 weeks following treatment and knee joints were processed for histological analysis. Collagen and cartilage degeneration were decreased by APS treatment, resulting in a significantly improved total joint score in APS-treated rats compared to those treated with the PBS control. No significant variations in gait analysis, weight gain, osteophyte score, or synovitis score were observed between APS- and PBS-treated animals. There were no adverse effects of APS reported in the study. Treatment with a single IA injection of APS reduced the cartilage degeneration that characterizes the progression of OA. Further studies are necessary to determine if APS can modify OA disease progression in humans. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2260-2268, 2017.

OBJECTIVE: To evaluate whether the post-surgery placement of the rectus sheath block analgesia (RSB) reduces the inflammatory response following surgery. The main hypothesis of our study was to find any correlation between patients\' pain experience, numeric rating scale (NRS) postoperatively and concentrations of inflammatory response biomarkers, such as interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, IL-10, IL-1β, in patients with benign disease and cancer.
METHODS: Initially, 46 patients with midline laparotomy were randomized to the placebo group (n=11) and to one of the three active groups; single-dose (n=12), repeated-dose (n=12) and continuous infusion (n=11) RSB analgesia groups. Plasma concentrations of high-sensitivity C-reactive protein (hs-CRP) and five interleukins (IL-1ra, IL-6, IL-8, IL-10, IL-1β) were measured at three time points; just before, immediately after and 24 h after operation. The primary end-point was to compare plasma concentrations of the hs-CRP and five interleukins in the placebo group and in the three different RSB analgesia groups in patients with benign disease and cancer.
RESULTS: The placebo group and three active groups were similar in terms of demographic variables and perioperative data. Of the anti-inflammatory cytokines, patients in the continuous infusion group had significantly higher IL-10 median values postoperatively than the three other study groups (p=0.029). In addition, patients in the three active groups combined had significantly higher IL-10 median values immediately after operation than the placebo group (p=0.028; in all patients with benign disease and cancer). There is a significant correlation between the individual values of NRS and IL-10 values postoperatively in the placebo group and the three active groups separately (r=0.40, p=0.03) and also a significant correlation between the individual values of the NRS scale and IL-1β values postoperatively in the placebo group and the three active groups separately (r=0.38, p=0.04).
CONCLUSIONS: Placement of RSB analgesia does not significantly reduce the inflammatory response biomarkers\' concentrations in patients with benign disease or cancer patients. A new finding in the present work is a significant correlation in the NRS scale versus plasma concentrations of anti-inflammatory cytokine IL-10 and pro-inflammatory cytokine IL-1β postoperatively suggesting that inflammation and pain are related.

BACKGROUND: There has been debate on which blood components should be included in autologous therapies. Autologous Protein Solution (APS) is a unique blood-derived therapy composed of concentrated white blood cells, platelets, and plasma to contain high concentrations of anti-inflammatory cytokines and anabolic growth factors to potentially address osteoarthritis. The primary aim of the exploratory secondary analysis was to identify characteristics of an Autologous Protein Solution (APS) that may correlate with improved Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and OMERACT-OARSI responder status after treatment of subjects with an intra-articular injection of APS.
METHODS: Eleven subjects were enrolled in a pilot study of a single intra-articular injection of APS in subjects with knee osteoarthritis. Two APS kits were processed per patient. The output of the first APS kit was injected intra-articularly. White blood cell (WBC) and cytokine concentrations were measured from the output of the second APS kit. WOMAC surveys were completed at baseline and at follow up visits. Linear regression analyses were performed on the blood components of APS with subject outcomes. Anderson-Darling analysis was used to determine whether the cytokine concentrations in whole blood and APS had a normal distribution. Either paired t-test analyses or Wilcoxon signed-rank analyses were performed for normal and non-parametrically distributed data, respectively.
RESULTS: The WBC concentration in APS was significantly (p < 0.05) and strongly (R(2) > 0.7) correlated with IL-1ra in APS but not significantly correlated with IL-1β. The ratio of IL-1ra to IL-1β in APS was significantly correlated with improved WOMAC pain scores one week and six months post-injection. 85.7 % of subjects whose APS had a IL-1ra:IL-1β ratio greater than 1000 or a WBC count greater than 30 k/μl were OMERACT-OARSI responders six months post-injection.
CONCLUSIONS: The correlations between the IL-1ra:IL-1β ratio and WBC concentration in a subject\'s APS and their WOMAC pain scores and classification as OMERACT-OARSI responders suggest the potential utility of these characteristics as diagnostic markers. Additional studies are ongoing to determine whether APS is safe and effective and to further evaluate the relationship between APS composition and clinical outcomes.
BACKGROUND: ( NCT01773226 ).

Familial Mediterranean fever (FMF) is a recessive autoinflammatory disorder. The balance between the pro-inflammatory cytokine IL-1β and its receptor antagonist IL-1RA plays an important role in the development of FMF. In order to determine a possible association of polymorphisms in IL-1β and IL-1RA genes with occurrence and/or severity of the disease, 42 genetically confirmed FMF patients and 42 controls were genotyped for IL-1β(-511C/T), IL-1β(-31T/C), IL1-1β(+3954T/C) and IL-1RA VNTR polymorphisms. IL-1β and IL-1RA levels were evaluated by multiplex ELISA in supernatants of PBMC cultures of 30 FMF patients with and without 24h stimulation of monocytes by LPS. The CC genotype and C allele at positions -31 and + 3954 of IL-1β gene were more frequent in FMF patients than in controls. FMF patients carriers of IL-1β(-31) CC genotype were associated with a 2-fold increase in LPS-induced IL-1β secretion as well as a higher disease severity score (11.2 ± 2.9) when compared to patients carrying the TC and TT genotypes (6.1 ± 2.1 and 4.5 ± 2.4, respectively). These results indicate that IL-1β gene polymorphisms at positions -31 and + 3954 may be associated with an increased risk for FMF. IL-1β(-31) contributes also to the severity of the disease, probably by modulating IL-1β synthesis.