Pregabalin inhibits proinflammatory cytokine release in patients with fibromyalgia syndrome.

Objectives: The main goal of the study was to investigate how pregabalin (PGB) affects proinflammatory cytokine release in patients with fibromyalgia syndrome (FMS). Patients and methods: This experimental research study was conducted with 85 female participants (mean age: 49.6±10.1 years; range, 30 to 73 years) between April 2020 and November 2020. Of the participants, 30 were FMS patients using PGB 150 mg/day for at least three months, 30 were FMS patients not using PGB, and 25 were healthy individuals. The detection of FMS was carried out according to the 2010 American College of Rheumatology diagnostic criteria. Levels of proinflammatory cytokines (interleukin [IL]-2, IL-6, IL-12, IL-17, interferon-gamma, and tumor necrosis factor-alpha) were measured by enzyme-linked immunosorbent assay. Results: Serum concentrations of proinflammatory cytokines were remarkably decreased in FMS patients using PGB (p<0.001) and were higher in patients with FMS not using PGB than in healthy subjects (p<0.001). The highest values of proinflammatory cytokines were found in the group of FMS patients not using PGB (p<0.001). Conclusion: These results indicate that PGB inhibits the release of proinflammatory cytokines, suggesting that it can be used as an anti-inflammatory agent in inflammatory cases.

Assessment of α9ß1 integrin as a new diagnostic and therapeutic target in Behcet's disease.

This study aimed to investigate the roles of α9ß1 integrin and its ligands in Behçet's disease (BD) by examining serum levels and gene expressions. 15 healthy controls and 30 BD patients (14 active and 16 inactive) were included in the study. Serum levels of ITGA9, ITGB1, TNC, OPN, VCAM-1, VEGF, TSP1, TGM2, Emilin-1, and vWF, were measured by ELISA. Gene expressions of α9ß1 (ITGA9 and ITGB1) and its ligands (TNC and SPP1) were evaluated by RT-PCR. Laboratory findings (CRP, ESR, HGB, WBC, RBC, neutrophil, lymphocyte, PLT, RDW, MPV, PCT, and HLA-B51) were obtained from the electronic database. Active BD patients had higher serum levels of α9ß1 integrin and its ligands than inactive patients and healthy controls. No significant difference was observed between healthy controls and inactive patients. Gene expressions of ITGB1 and SPP1 were increased in both patient groups compared to healthy controls. ITGA9 and TNC gene expression levels were lower in the active group than in the inactive group. No noticeable differences were found in ITGB1 and SPP1 gene expressions between the patient groups. BD patients exhibited elevated CRP, ESR, WBC, neutrophil, PLT, and PCT levels, while HGB, RBC, and RDW values were lower than healthy controls. Active patients had higher CRP, ESR, WBC, neutrophil, and PLT levels. Significant positive correlations were found between CRP, ESR, WBC, neutrophil, PLT, PCT and serum levels of α9ß1 integrin and its ligands. Increased release of α9ß1 integrin and its ligands is associated with BD, suggesting their potential as markers for disease severity.

Investigation of IL-35 and IL-39, New Members of the IL-12 Family, in Different Clinical Presentations of Brucellosis.

Brucellosis is significantly influenced by the interactions between the causative Brucella bacteria and host immunity. Recently identified cytokines have been described for their immunomodulatory effects in numerous inflammatory, autoimmune and infectious diseases. Some of them are new members of cytokine superfamilies, including several members of the IL-12 superfamily (IL-35, IL-39). The major purpose of the present study was to investigate the role of these new immunomodulatory cytokines in Brucella infections. The levels of IL-35 and IL-39 in the serum of 40 acute and 40 chronic brucellosis patients and 40 healthy controls were measured by ELISA. The mRNA levels of IL-35 and IL-39 in PBMCs were detected by RT-qPCR. Both IL-35 and IL-39 serum concentrations were significantly higher in healthy control subjects than in brucellosis patients, and IL-35 and IL-39 serum levels of chronic brucellosis patients were higher than those of acute cases. It was also found that the expression of Ebi3/IL-12A (IL-35 genes) and Ebi3/IL-23A (IL-39 genes) was upregulated in chronic brucellosis patients compared to healthy controls. Moreover, the expression of the Ebi3/IL-12A and Ebi3/IL-23A genes was lower in patients with acute brucellosis than in patients with chronic brucellosis. Overall, this study showed that IL-35 and IL-39 are positively correlated in brucellosis and significantly decreased during the disease. Significantly lower levels of IL-35 and IL-39 in acute brucellosis than in chronic brucellosis and healthy controls suggest that these cytokines may play a key role in suppressing the immune response to brucellosis and its progression to chronicity.

IL-35 and IL-39, new members of the IL-12 cytokine family, are immunomodulatory cytokines characterized as anti-inflammatory and pro-inflammatory, respectively.In acute and chronic brucellosis, serum IL-35 and IL-39 are significantly decreased.In acute brucellosis, serum IL-35 are significantly lower than in chronic brucellosis, suggesting that this cytokine may play a role in chronification.A positive correlation was found between IL-35 and IL-39 in acute and chronic brucellosis, suggesting that the common protein subunit Ebi may be suppressed.According to the results of this study, IL-35 and IL-39 may play a role in the pathogenesis of brucellosis.

Evaluation of the Relationship between Proinflammatory Cytokine Levels and Clinical Findings of Fibromyalgia Syndrome.

BACKGROUND: Immune system has an important effect on pain-related disorders such as fibromyalgia syndrome (FMS). There is no specific laboratory technique for the diagnosis of FMS, but measuring serum proinflammatory cytokines may help. OBJECTIVE: The purpose of our study was to determine the serum levels of immune mediators and their relationship with FMS symptoms. METHODS: 25 healthy individuals and 29 FMS patients receiving pregabalin 150 mg/day for a minimum of 3 months were included in this study. FMS patients were diagnosed according to diagnostic criteria of the American College of Rheumatology (ACR 2010). Widespread pain index (WSI), fatigue, waking unrefreshed, cognitive symptoms, somatic symptoms, and Fibromyalgia Impact Questionnaire (FIQ) scores were evaluated in patients with FMS. Serum levels of proinflammatory cytokines (IL-2, IL-6, IL-12, IL-17, IFN-γ, TNF-α) were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Proinflammatory cytokine levels were higher in the control group than in patients with FMS (P<0.05). A positive correlation was found between age and WSI (P=0.037). In addition, a significant positive relationship was determined between IL-17 level and waking unrefreshed (P=0.049). There was no significant relationship between other cytokines and clinical findings. CONCLUSION: Lower proinflammatory cytokine levels identified in FMS patients may be related to pregabalin treatment, and there may be an impairment in the inflammatory response. On the contrary, IL-17 showed a positive correlation with waking unrefreshed.