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Background and Objective: Atherosclerosis, a chronic and progressive inflammatory disease, is triggered by the activation of endothelial cells followed by infiltration of innate and adaptive immune cells including monocytes and T cells in arterial walls. Major populations of T cells found in human atherosclerotic lesions are antigen-specific activated CD4+ effectors and/or memory T cells from Th1, Th17, Th2 and Treg subsets. In this review, we will discuss the significance of T cell orchestrated immune inflammation in the development and progression of atherosclerosis. Discussion: Pathogen/oxidative stress/lipid induced primary endothelial wound cannot develop to a full-blown atherosclerotic lesion in the absence of chronically induced inflammation. While the primary inflammatory response might be viewed as a lone innate response, the persistence of such a profound response over time must be (and is) associated with diverse local and systemic T cell responses. The interplay between T cells and innate cells contributes to a phenomenon called immuneinflammation and has an impact on the progression and outcome of the lesion. In recent years immuneinflammation, an old term, has had a comeback in connecting the puzzle pieces of chronic inflammatory diseases. Conclusion: Taking one-step back and looking from afar at the players of immune-inflammation may help us provide a broader perspective of these complicated interactions. This may lead to the identification of new drug targets and the development of new therapies as well as preventative measures.

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The elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes, especially in pro-inflammatory states such as surgical injuries and severe hemorrhages. Therefore, it was hypothesized whether NLR value at the time of admission could be a prognostic indicator of hospital mortality in trauma patients. This retrospective cohort study was conducted on 865 trauma patients referred to Rajaee Hospital between April 2016 and July 2019. The NLR value was calculated at the time of admission, and receiver operating characteristics (ROC) curve analysis was used to determine the cut-off point value of admission NLR related to hospital mortality of trauma patients. Furthermore, Kaplan-Meier survival analysis and Cox regression models have been applied to determine the effectiveness and prognostic potential of the admission NLR in the hospital mortality of trauma patients. The median age of the trauma patients was 32 years with an interquartile range (IQR) of 23 to 48 years, and most of them were male (83.9%). Also, trauma patients had a median injury severity score (ISS) of 9 (IQR=4-16) and a median Glasgow coma scale (GCS) of 14 (IQR=9-15). The cut-off value for admission NLR was 5.27 (area under the curve: 0.642, 95%CI: 0.559-0.726, p=0.001). In Kaplan-Meier survival analysis, the admission NLR>5.27 was an indicator of hospital mortality in trauma patients (p=0.001). Multivariate Cox regression models demonstrated that trauma patients with an admission NLR>5.27 had a 2.33-fold risk of hospital mortality (hazard ratio=2.33, 95%CI: 1.02-5.38, p=0.041). Furthermore, the admission NLR>5.27 was associated with a higher risk of hospital mortality in trauma patients with age≥65 years, systolic blood pressure≤90 mmHg, blood potassium>4.5 mmol/L, blood sodium>144 mEq/L, blood potential hydrogen (pH)≤7.28, GCS≤8, ISS>24 and blood base excess≤-6.1 mEq/L. The NLR value greater than 5.27 at the time of admission was associated with poorer outcomes, and it can be considered an independent prognostic indicator of hospital mortality in trauma patients.

Although cellular and molecular mediators of the immune system have the potential to be prognostic indicators of disease outcomes, temporal interference between diseases might affect the immune mediators, and make them difficult to predict disease complications. Today one of the most important challenges is predicting the prognosis of COVID-19 in the context of other inflammatory diseases such as traumatic injuries. Many diseases with inflammatory properties are usually polyphasic and the kinetics of inflammatory mediators in various inflammatory diseases might be different. To find the most appropriate evaluation time of immune mediators to accurately predict COVID-19 prognosis in the trauma environment, researchers must investigate and compare cellular and molecular alterations based on their kinetics after the start of COVID-19 symptoms and traumatic injuries. The current review aimed to investigate the similarities and differences of common inflammatory mediators (C-reactive protein, procalcitonin, ferritin, and serum amyloid A), cytokine/chemokine levels (IFNs, IL-1, IL-6, TNF-α, IL-10, and IL-4), and immune cell subtypes (neutrophil, monocyte, Th1, Th2, Th17, Treg and CTL) based on the kinetics between patients with COVID-19 and trauma. The mediators may help us to accurately predict the severity of COVID-19 complications and follow up subsequent clinical interventions. These findings could potentially help in a better understanding of COVID-19 and trauma pathogenesis.

The relationship between high levels of anti-Varicella Zoster Virus (VZV) IgG in cerebrospinal fluid (CSF) and cerebrovascular atherosclerosis commends a possible similar association in other vessels. We aimed to investigate the association of VZV-seropositivity with coronary artery atherosclerosis. We recruited 88 newly diagnosed patients with more than 50% stenosis in at least one of the main coronary arteries. As the control group, 99 age-matched individuals with normal/insignificant coronary artery findings were included. Clinical, paraclinical, and demographical data were gathered at the time of sampling. High‐sensitivity C‐reactive protein (hsCRP) levels were measured by nephelometry. VZV-seropositivity was determined by measuring of anti-VZV IgG level in plasma. Multivariable logistic regression was used to evaluate the correlation of data with coronary vascular atherosclerosis. The frequency of VZV-seropositivity was significantly higher in the atherosclerosis group compared to the controls (OR=1.88; 95%CI=1.03-3.44). The plasma levels of anti-VZV IgG were significantly higher in patients with atherosclerosis (Median=2.70, IQR=1.53-4.30 AU/mL) than in the controls (Median=2.10, IQR=1.70-3.10 AU/mL, p=0.034). The hsCRP levels in patients and controls were 5.19±2.00 and 1.51±1.07 mg/L, respectively. The correlation between hsCRP and anti-VZV IgG level in plasma was observed (r=0.40, p<0.001). The levels of hsCRP and anti-VZV IgG increased based on the number of diseased vessels but only the difference in hsCRP levels reached a significant level (p<0.001 and p=0.168, respectively). Our data suggest that VZV-seropositivity and hsCRP elevation jointly increase the risk of atherosclerosis. The multifactorial nature of atherosclerosis; however, leaves more options for the inflammatory milieu to be generated.

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Objective:Brain tumors are of high mortality and morbidity for which there is still no cure. The TNF family cytokine, A Proliferation Inducing Ligand (APRIL), is shown to help proliferation and development of tumor cells. We assessed serum levels of APRIL in patients with glioma, meningioma and schwannoma in comparison to healthy individuals.Methods:Peripheral blood samples of 68 patients with brain tumors, divided into three groups of gliomas (n=25), meningiomas (n=30) and schwannomas (n=13), as well as 45 healthy individuals were obtained. Serum samples were prepared and stored in -40°C until usage. Using a commercial ELISA method, APRIL concentration was measured in each serum sample. The obtained data were then analyzed using SPSS software.Results:APRIL serum levels were higher in all patients compared to the controls (P<0.001). Moreover, APRIL serum levels were higher in each of the tumor bearing groups (gliomas, meningiomas and schwannomas) in comparison to the controls (P<0.001, <0.001 and =0.001, respectively). Comparing APRIL between the patients groups showed no significant difference. Age and gender showed no significant correlation with serum APRIL levels, although the age of patients in glioma group was significantly lower than controls (P=0.017). The serum APRIL levels in gliomas with histological grade showed no difference, but in meningiomas, it was lower in tumors with higher grades (P= 0.011).Conclusion:Increased serum levels of APRIL in patients with meningioma and schwannoma as well as glioma may indicate a common role of this cytokine in brain tumors.