Cytokines and inflammation

BACKGROUND: The human papillomavirus is an etiological factor and a biological carcinogen in tumor lesions and cancer. Currently, there are several known possible mechanisms of immune evasion of human papillomavirus. Therefore, early methods for diagnosing papillomavirus infection and effective treatments.

AIM: To analyze the cytokine profile should be established of dendritic cells in response should be determined to stimulation by peptide L2 of human papillomavirus type 16 in vitro.

METHODS: Dendritic cell cultures were obtained from the blood of donors without signs of the human papillomavirus infection in history. A culture without stimulation was used as a control. As experimental groups, cultures synthesized peptide with L2 of the human papillomavirus type 16 were used. Enzyme-linked immunosorbent assay was used to determine the levels of pro- and anti-inflammatory cytokines.

RESULTS: In comparison with spontaneous response in the control group after inoculation with peptide L2 of human papillomavirus type 16, increased IL-10, MCP-1, VEGF, IL-6, and IFN-γ concentrations and significant changes in IL-1β, IL-4, IL-8, IFN-α, and TNF-α concentrations were not detected.

CONCLUSIONS: The results confirm the ability of the human papillomavirus to evade the antiviral immune response by affecting the synthesis of several cytokines.

BACKGROUND: Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) affect more than 6.8 million people. The key factor in the immunopathogenesis of these diseases is the intestinal wall infiltration by various immunocompetent cells and their proinflammatory cytokine production.

AIM: To compare the levels of 14 cytokines in the coproextracts of patients with IBD with various disease activities.

MATERIALS AND METHODS: The examined cohort comprised 30 children with CD, 33 with UC, and 20 healthy children (control group). UC and CD were diagnosed based on generally accepted clinical and endoscopic criteria. The concentrations of 14 cytokines (IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, and TNF) in aqueous-salt coproextrates were determined using the multiplex method (MagPix, BioRad, USA).

RESULTS: The levels of all studied cytokines were significantly increased in all sick children, even in remission, compared with the control group. The concentration of proinflammatory cytokines (TNF, IL-1β, IL-6, IL-17A, and IL-17F) consistently decreased with the decrease in disease activity in the coproextracts of patients with CD and UC. Furthermore, the IL-22, IL-33, and IL-10 levels increased as the inflammation activity decreased.

CONCLUSIONS: The lack of normalization of cytokine levels in remission raises the question of the need for further study of IBD immunopathogenesis and the search for new therapeutic approaches.

INTRODUCTION: Neurodegenerative diseases are common chronic disorders that are associated with progressive damage to the nervous system. The role of the immune system in the development of neurodegenerative diseases was confirmed by data on the activation of microglia, the presence of an imbalance in the composition and phenotype of peripheral immune cells, and the presence of humoral immunity disorders and intestinal microbiota dysbiosis in patients with this pathology.

DISCUSSION: Inflammation has been observed to play a key role in the pathogenesis of diseases associated with progressive damage to the nervous system. The article analyzes the mechanisms in the development of “subclinical” chronic inflammation that leads to development of old-age-related diseases, including neurodegenerative pathology. At least three groups of factors associated with old age play a role in the formation of a proinflammatory status: mitochondrial dysfunction, development of an age-related proinflammatory status of the immune system, and chronic stress. Mitochondrial dysfunction is primarily associated with disruption of mitophagy processes: failure of quality control mechanisms as a result of disruption of mitophagy processes leads to the accumulation of terminally damaged mitochondria, which become a threat to cell survival. Inadequate removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and the development of inflammatory diseases. A high level of deletions in the mitochondrial genetic apparatus that accumulates with age inevitably leads to increased formation of reactive oxygen species, which in turn are assumed as one of the leading activators of the cytosolic NLRP3 protein, the primary component of inflammasomes. Increased inflammasome formation eventually leads to caspase-1-dependent production of proinflammatory interleukins. Age-related inflammatory imbalance is associated with the fact that the immune system, the main protective mechanism characterized by the inflammatory response, copes with constant antigenic attacks. However, over time, upon reaching a certain threshold, the reaction of the immune system becomes excessive, characterized by increased production of coagulation factors, proinflammatory cytokines, acute phase proteins of inflammation, prostaglandins, and leukotrienes.

CONCLUSIONS: Immunological changes that develop during chronic (long-term) stress are the result of a disruption of the homeostatic connection between the neuroendocrine and immune systems, leading to the formation of an inflammatory background that complements the “proinflammatory status” that develops as a result of age-related changes in the immune system and disruption of mitophagy mechanisms.