IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.
Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient's MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.
Introduction: Periodontitis is one of the most common causes of tooth loss worldwide. Recently, special attention has been paid to natural medication for its treatment. For this purpose, propolis (bee glue) activity has also been investigated. Its antibacterial properties are mainly attributed to flavonones pinocembrin, flavonols galangin and to the caffeic acid phenethyl ester. This study is aimed at evaluating the antimicrobial effects of propolis from Pakistan on 35 clinical isolates of pigmented anaerobic periodontal pathogens.Methods: This study was conducted in the Microbiology department, University of Health Sciences, Lahore, Pakistan. Pathogens included were Porphyromonas asaccharolytica (n=9), Porphyromonas gingivalis (n=13), Prevotella intermedia (n=9), Prevotella melaninogenica (n=4). Minimum inhibitory concentration (MIC) to three antibiotics was obtained by E-test method. All strains were sensitive to amoxicillin plus clavulanic acid and metronidazole, but 100% of P asaccharolytica and P melaninogenica strains displayed intermediate resistance to tetracycline while 69.2% P gingivalis and 100% P intermedia strains exhibited complete resistance to tetracycline. Screening for antibacterial activity of propolis extract was done by agar well diffusion assay, and all strains were found sensitive to ethanolic extract of propolis.Results: MIC was obtained by agar incorporation technique with values ranging from 0.064 to 0.512 mg/ml. It was also noticed that percentage yield of ethanolic extract of propolis prepared from ultrasonic extraction method was higher compared to extract obtained with maceration.Conclusion: These results indicate that propolis from this region has potent antimicrobial activity against pigmented anaerobic periodontal pathogens. Taking into consideration the increasing resistance in anaerobic bacteria, this effective antimicrobial activity of propolis gives hope in the treatment of oral cavity diseases.
Background We hypothesized that anti-thyroid antibodies are more often positive in individuals with deranged thyroid profile. Methods This prospective cohort was done in Immunology Department, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from Jan 2017 to Oct 2017. All the samples that were referred to us for testing anti-thyroid antibodies (anti-TPO or anti-TG antibodies) and thyroid profile were included in the study. There were no exclusion criteria. Tests for anti-thyroid antibodies were performed by ELISA and thyroid profile by chemiluminescence. SPSS 23.0 was used for statistical analysis. Results Over a course of a ten-month study period, we received a total of 316 serum samples for anti-TPO/TG antibodies along with thyroid profile testing (TSH). These included 115 males (36.4%) and 201 females (63.6%). Their age ranged from 3 to 89 years (mean ± SD, 42.22 ± 18.09). Anti-TPO antibodies were more often positive when TSH was deranged (p value 0.001). Anti-TPO antibodies are more often raised in females, in terms of both prevalence (p 0.001) and mean rank (p 0.002). Conclusion As anti-thyroid antibodies are more often present when TSH is deranged, such individuals should be screened for anti-thyroid antibodies. This importance of screening is compounded by the fact that anti-thyroid antibodies may be positive in a significant percentage of elderly people.
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