Immunoregulation
Volume:3 Issue: 2, Winter 2020

As I noted in my previous editorial, It is necessary to examine the immunological aspects of COVID-19. Thus, in order to identify the underlying mechanisms, design appropriate treatment protocols, and effective vaccination, we started to conduct a multicenter cohort study entitled “Iran-Cohort Study of COVID-19 Immunology and Immunopathology”. This comprehensive multicenter cohort study is underway at Immunoregulation Research Center, Shahed University, Tehran, Iran.

In recent years, the microbiome has been recognized as a key regulator of immune responses. Evidence suggests that changes in the microbiome can lead to chronic disease and even exacerbation of the disease. Impairment of innate immunity resulting from microbial incompatibility may worsen host susceptibility to infection and exacerbate chronic lung diseases. Specific microbes play a key role in improving immune responses and microbial incompatibility is involved in chronic lung diseases such as asthma, chronic obstructive pulmonary disease, and Cystic Fibrosis (CF). CF is an extremely complex disease that results from a gene mutation. Lack of expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) has late complications. Incompatibility in lung microbiota is associated with chronic lung diseases, but it is not determined whether this incompatibility can cause health problems or ineffective regulation of immune response create the disease and its progression. In the CF, due to the deficiency of the immune system, many opportunistic microorganisms, including Pseudomonas. aeruginosa or Staphylococcus aureus are colonized in the patient’s lung and due to an immunodeficiency causedby a defect in the system CFTR, lungs are unable to clear the bacteria that leads to severe pulmonary complications and respiratory and digestive problems in such patients. Therefore, in these patients, the microbiome contributes to dysfunctional immune responses and disease exacerbations. This review summarizes the impact of the microbiome on host immune responses and its relationship with CF to explore the role of the microbiome in causing CF.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pandemic virus, a global concern, and has threatened human health. This virus binds to the Angiotensin-Converting Enzyme 2 (ACE2) that is expressed on different cells, especially on the alveolar cells. So the virus can enter the lung cells and causes respiratory syndromes. In Coronavirus Disease 2019 (COVID-19)  that is caused by SARS-CoV-2, respiratory failure, and acute inflammation is the main cause of death. According to several reports, multiple factors, such as Neutrophils to Lymphocytes Ratio (NLR) have prognostic potentials in COVID-19. This study aims to review this parameter to have a better prediction about the condition of the patients and their treatments. According to this review, the NLR ratio that is related to the innate immune responses and inflammation can be helpful in the discrimination of severe from non-severe cases of COVID-19 patients.

Sepsis is a systemic inflammatory disease in response to the pathogens that leads to vital organ failures the failure of vital organs. Appropriate animal models should be developed to measure the effectiveness of therapeutic methods. Cecal Ligation and Puncture (CLP) is the most widely used methods of creating the sepsis model. Some variables interfere in the creation of the CLP model which terminated to result in an unrepeatable dynamic of the inflammatory responses. The current research, suggests presents the simultaneous study of inflammatory responses in serum and liver as a criterion for determining the inflammatory status of the CLP model. CLP model was induced in 15 female C57bl/6 mice. IL-6, TNF-α, IL-10, and TGF-β1 cytokines levels were measured at 24, 48, and 72 hours after CLP induction in both serum and liver tissue by ELISA method. Serum levels of liver enzymes were analyzed by the clinical chemistry analyzer. All studies were performed in healthy mice as well. The results were reported as Mean±SD. The levels of IL-10 and TGF- β1 in the liver is were significantly (P≤0.05) higher than serum. The production of IL-10 and TGF- β1 in the serum and liver reaches its maximum at peaked 24 and 72 hours after CLP induction. The level of TNF-α in the liver is was significantly (P≤0.05) higher than serum with a maximum production 24 hours after CLP induction. Serum is not a good representative of the inflammatory condition in sepsis. Therefore, it is suggested that local inflammatory responses be considered in evaluating the model, and the determination of drug efficacy.

Aging is associated with attenuation of immune responses. Studies show that old people are vulnerable to infectious diseases such as influenza. α-Tocopherol as an immunomodulator affects immune responses. In the present study, the effect of α-tocopherol, on lymphocyte responses i.e. interferon-gamma (IFN-γ), Tumor Necrosis Factor-alpha (TNF-α), and nuclear factor-κB (NF-κB)  in elderly individuals was evaluated. Heparinized blood samples were prepared from 10 elderly individuals (n=10, age >80 years) as the experimental group and 10 young individuals (n= 10, 20-40 years) as the control group. The separated Peripheral Blood Mononuclear Cells (PBMCs) of aged and young individuals were used for treatment with 2 μg/mL of α-tocopherol and 2 μg/mL of Purified Protein Derivative (PPD) after 12 and 24 h incubation period. After isolation of total RNA and synthesize of cDNA, the gene expressions of IFN-γ, TNF-α, and NF-κB were evaluated by real-time PCR method. β-Actin gene was considered as the internal control gene. Results showed that treatment with α-tocopherol increased the IFN-γ expression in old and young lymphocyte groups. The mRNA level of NF-κB increased in the PPD group after 12 h in both old and young groups (p <0.05). There were no alterations in TNF-α expression in both groups. It seems that α-tocopherol is effective in the promotion of cytokine responses in old individuals and may be useful as a supplement for improving the immune system of elderly people.

It seems that Vinca. herbacea has an anti-tumor effect. Here, the immunotherapeutic effect of this compound is assessed against human ovarian cancer (SKOV3) cells because of the high incidence of this tumor in women. The cytotoxic activity of V. herbacea extract against human ovarian cancer (SKOV3) cells was determined by MTT assay. The apoptosis-inducing potential of V. herbacea extract was investigated using the FITC-V Annexin kit. The Matrigel invasion assay was used to investigate the ability of V. herbacea extract in reducing ovarian cancer cells invasion. Real-time PCR using specific primers was performed to investigate the expression of angiogenesis (VEGFR1, VEGFR2, and VEGF-A), apoptosis (Bcl-2 and Bax), and metastasis (MMP2 and MMP9) genes. V. herbacea caused a significant cytotoxic effect against human ovarian cancer cells in a dose-dependent manner. V. herbacea induced apoptosis in SKOV3 cells through caspase-3 activation and an increase in the expression ratio of Bax/Bcl-2. V. herbacea inhibited cancer cells’ angiogenesis, which was evident by the significant reduction in the expression of angiogenesis-related genes, including VEGF, VEGFR-1, and VEGFR-2. Besides, V. herbacea inhibited cancer cell adhesion and invasion. V. herbacea extract elicits a robust cytostatic effect in SKOV3 cells by modulating the activity and or the expression of proteins regulating the process of cellular apoptosis, adhesion invasion, and angiogenesis.

Anticancer effects of Lactobacillus acidophilus, as a probiotic bacterium, have been indicated in several studies. There are common therapeutic options for bladder cancer treatment; however, their side effects and recurrence of disease are considerable. Therefore, complementary medication is essential and it must be safe and effective. In the present research, we assessed the anti-tumor activity of Lactobacillus acidophilus (LB) on the bladder cancer cell line by evaluating the apoptosis mechanism.

EJ138 bladder cancer cell line was provided and the cytotoxicity level of LB was evaluated with various concentrations after 24, 48, and 72 h. To evaluate the apoptosis effect, the gene expression of Bax, BCL2, and TNF-α was assessed using real-time PCR.

The optimum concentration of the cytotoxicity level was 12.5μg/mL at 24, 48, and 72 h. Bax expression was upregulated in tumor cells treated with LB alone and the mixture of LB and BCG (LB/BCG) as compared to the control group after 24 and 48 h. Also, the mRNA level of TNF-α increased in treated cells with LB and LB/BCG compared to the control group. BCL2 expression did not show a significant difference between experimental groups versus the control group.

Our findings showed that LB has a synergistic effect with BCG through increasing apoptotic gene expression and TNF-α cytokine. Besides, at 48 h treatment, the apoptosis effect is more than 24 h. Thus, it seems that the mode of action of LB is time-dependent.

The nervous, endocrine, and immune systems contribute to the response and dynamic adaption to various stresses. Activation of the hypothalamic-pituitary-adrenal axis has been demonstrated in various active critical illnesses. Novel Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), is a disease with age and gender disparities.

In this study, a total of 125 consecutive inpatients with COVID-19 admitted to Imam Khomeini Hospital Complex from February 12, 2020, to April 4, 2020, were enrolled. The severity of patients was classified into three subgroups based on the types of oxygen therapies. Dehydroepiandrosterone Sulfate (DHEA-S) and cortisol levels were measured in serum of inpatients with Siemens kit.

While the increase in cortisol level was not significant in COVID-19 patients, the DHEA-S level and DHEA-S/cortisol ratio significantly decreased in the patients with the increase in severity of the disease.

We proposed that the supplementation of DHEA, the precursor of both androgens and steroids, may ameliorate adverse outcomes of COVID-19 disease and improve COVID-19 patients’ ability to survive.