Background Interleukin‐6 (IL‐6) is produced by and impacts different cell types in human. IL‐6 is associated with different diseases and viral infections, including COVID‐19. To our knowledge, no normal values were reported for IL‐6 in the blood of healthy individuals. We have reviewed and performed a meta‐analysis on a total of 140 studies, including 12,421 values for IL‐6 in the blood of healthy adult donors. Among these studies, 83 did not report a mean value and the standard deviation. Therefore, for the statistical analysis, we used the values reported in 57 studies, which included 3166 values for IL‐6. Results The reported values for IL‐6 in the blood of healthy donors varied between 0 and 43.5 pg/ml. The pooled estimate of IL‐6 was 5.186 pg/ml (95% confidence interval [CI]: 4.631, 5.740). As the age increased by 1 year, IL‐6 values increased by 0.05 pg/ml (95% CI: 0.02, 0.09; p < .01). Though the heterogenicity, as determined by I2 statistics, was high in our study, the differences in IL‐6 values are still at the level of a few pg/ml, which might be related to the differences in the conditions that influence IL‐6 production in the healthy population. Conclusions This is the first meta‐analysis reporting the levels of IL‐6 in the blood of healthy donors based on a large number of studies and donors. Therefore the 95% CI values determined in our study could well serve as a reference range for quick decision‐making in clinical interventions, particularly those aiming to inhibit IL‐6, especially urgent interventions, for example, COVID‐19.

BackgroundThe failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers.MethodsDouble staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas.ResultsChronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade.ConclusionThe upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis.

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Background: Increasing rate of resistant infections is a challenge to healthcare negatively impacting therapeutic and financial outcomes. Targeted antimicrobial stewardship interventions are needed to counteract this global crisis. On large scale, we sought to identify the prevalence of resistant pathogens and their susceptibility pattern in Northern Oman. Material and method: Retrospective analysis of all isolates processed by Suhar Hospital microbiology laboratory between Jan1st, 2016 and Dec31st, 2017. Organism identification, susceptibility and phenotyping were performed following CLSI standards and duplicate isolates were excluded. Pertinent microbiological data were collected and analyzed. Results: Of 15,733 samples included, Gram-negative bacteria predominate by 67.76%, Gram-positive (29%) and Candida species (2.63%). Frequently isolated Gram-negative bacteria were Escherichia coli (32.39%), Pseudomonas aeruginosa (22.16%), Klebsiellapneumoniae (19.97%) and Acinetobacter baumannii (5.22%), there was virtually no resistance to colistin and tigecycline, while a growing resistance toward ciprofloxacin and meropenem was observed. Resistant E. coli and K. pneumoniae were isolated from bloodstream infection (12%). While Gram-positives were MSSA (27.23%), Streptococcus agalactiae (25.36%), MRSA (16.10%) and CoNS (12.1 %), they were almost universally susceptible to daptomycin and linezolid with low resistance (8~20%) to clindamycin. Approximately, 50% of Staphylococci (MRSA and CoNS) required vancomycin treatment. Conclusion: Study findings should guide targeted stewardship interventions to optimize antibiotic prescriptions. Empirical treatment options should be revised, drug-bug match therapy instituted promptly and newer agents considered. Prescribing restriction of formulary antimicrobials that still retain their activity towards bugslike colistin, linezolid and tigecycline-is a mandatory action. Review empiric use of ciprofloxacin and meropenem to counteract growing resistance.

AimThe lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression.MethodsCD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry.ResultsThe count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas.ConclusionsOur results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.

: Metabolites produced by bacteria can influence the immune system. These metabolites are produced by pathogenic bacteria as well as the friendly microbiota. This review sheds light on the major bacterial metabolites and their structures. It also describes the capacity of these molecules to stimulate and inhibit the immune responses in a way that affects their capacity to control different diseases.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.