Cytokine status indicators in children with acute respiratory viral infections after treatment with intranasal interferon-based medicine

Objective: to study the dynamics of local and systemic cytokine production in children with different clinical forms of acute respiratory viral infections (ARVI), including COVID-19, and to assess the effectiveness of local interferon-based therapy.Patients and methods: The study included 180 patients aged from 1 month to 17 years with сonfirmed acute respiratory viral infections (ARVI), including COVID-19. Patients were divided into 2 groups (main and control) of 90 people each. In the main group patients received the intranasal interferon-based medicine Grippferon® in addition to the basic therapy, the control group patients received only basic therapy. The cytokine status was assessed by the content of IFN-α and -γ, IL-1β, IL-8, IL-4, IL-10, IL-17 in blood serum and in nasopharyngeal secretions by enzyme immunoassay kits ("Cytokine", St. Petersburg).Results: Statistically significant differences were revealed in the systemic and local content of individual cytokines in ARVI of different etiologies, depending on the level of damage to the respiratory tract. The use of the interferon-based medicine Grippferon® for intranasal use in children in the early stages of ARVI, including COVID-19, helps to decrease the high content of cytokines IL-1β and IL-8 in the nasopharynx by reducing the viral load. As a result, the duration of catarrhal disease symptoms and intoxication was also significantly reduced as well as the pathogen elimination time.

Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease

Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4+ T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.

Sequential Changes in the Mesenteric Lymph Node Microbiome and Immune Response during Cirrhosis Induction in Rats

ABSTRACT Whether the interaction between the gut microbiota and the immune response influences the evolution of cirrhosis is poorly understood. We aimed to investigate modifications of the microbiome and the immune response during the progression of cirrhosis. Rats were treated with carbon tetrachloride (CCl4) to induce cirrhosis. We then assessed microbiome load and composition in stool, ileocecal contents (ICCs), mesenteric lymph nodes (MLNs), blood, and ascitic fluids (AFs) at 6, 8, and 10 weeks or ascites production and measured cytokine production in MLNs and blood. The microbiome of MLN, blood, and AF showed a distinct composition compared to that of stool and ICCs. Betaproteobacteria (Sutterella) were found associated with the appearance of a decompensated state of cirrhosis. Microbial load increased and showed a positive correlation with the relative abundance of pathobionts in the MLN of decompensated rats. Among several genera, Escherichia and “Candidatus Arthromitus” positively correlated with elevated levels of systemic proinflammatory cytokines. “Candidatus Arthromitus,” a segmented filamentous bacteria, was detected in ICC, MLN, and AF samples, suggesting a possible translocation from the gut to the AF through the lymphatic system, whereas Escherichia was detected in ICC, MLN, AF, and blood, suggesting a possible translocation from the gut to the AF through the bloodstream. In the present study, we demonstrate that microbiome changes in distinct intestinal sites are associated with microbial shifts in the MLNs as well as an increase in cytokine production, providing further evidence of the role the gut-liver-immunity axis plays in the progression of cirrhosis. IMPORTANCE Cirrhosis severity in patients was previously shown to be associated with progressive changes in the fecal microbiome in a longitudinal setting. Recent evidence shows that bacterial translocation from the gut to the extraintestinal sites could play a major role in poor disease outcome and patient survival. However, the underlying mechanisms involving the microbiota in the disease progression are not well understood. Here, using an animal model of cirrhosis in a longitudinal and multibody sites setting, we showed the presence of a distinct composition of the microbiome in mesenteric lymph nodes, blood, and ascitic fluid compared to that in feces and ileocecal content, suggesting compartmentalization of the gut microbiome. We also demonstrate that microbiome changes in intestinal sites are associated with shifts in specific microbial groups in the mesenteric lymph nodes as well as an increase in systemic cytokine production, linking inflammation to decompensated cirrhosis in the gut-liver-immunity axis.

Identification of (poly)phenol treatments that modulate the release of pro-inflammatory cytokines by human lymphocytes

Diets rich in fruits and vegetables (FV), which contain (poly)phenols, protect against age-related inflammation and chronic diseases. T-lymphocytes contribute to systemic cytokine production and are modulated by FV intake. Little is known about the relative potency of different (poly)phenols in modulating cytokine release by lymphocytes. We compared thirty-one (poly)phenols and six (poly)phenol mixtures for effects on pro-inflammatory cytokine release by Jurkat T-lymphocytes. Test compounds were incubated with Jurkat cells for 48 h at 1 and 30 µm, with or without phorbol ester treatment at 24 h to induce cytokine release. Three test compounds that reduced cytokine release were further incubated with primary lymphocytes at 0·2 and 1 µm for 24 h, with lipopolysaccharide added at 5 h. Cytokine release was measured, and generation of H2O2 by test compounds was determined to assess any potential correlations with cytokine release. A number of (poly)phenols significantly altered cytokine release from Jurkat cells (P<0·05), but H2O2 generation did not correlate with cytokine release. Resveratrol, isorhamnetin, curcumin, vanillic acid and specific (poly)phenol mixtures reduced pro-inflammatory cytokine release from T-lymphocytes, and there was evidence for interaction between (poly)phenols to further modulate cytokine release. The release of interferon-γ induced protein 10 by primary lymphocytes was significantly reduced following treatment with 1 µm isorhamnetin (P<0·05). These results suggest that (poly)phenols derived from onions, turmeric, red grapes, green tea and açai berries may help reduce the release of pro-inflammatory mediators in people at risk of chronic inflammation.

Caspase-11 Modulates Inflammation and AttenuatesToxoplasma gondiiPathogenesis

Toxoplasma gondiiis an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection withT. gondiiresults in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1βand IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase-11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilizedAsc−/−andCasp11−/−mice and infected these animals withT. gondii. Our data indicates that caspase-11 modulates the innate immune response toT. gondiithrough a mechanism which is distinct from that currently described for the canonical inflammasome.Asc−/−mice demonstrated increased disease pathogenesis during the acute phase ofT. gondiiinfection, whereasCasp11−/−mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1β. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis.

Vitamin A-Deficient Hosts Become Nonsymptomatic Reservoirs of Escherichia coli-Like Enteric Infections

Vitamin A deficiency (A−) remains a public health concern in developing countries and is associated with increased susceptibility to infection.Citrobacter rodentiumwas used to model humanEscherichia coliinfections. A−mice developed a severe and lethal (40%) infection. Vitamin A-sufficient (A+) mice survived and cleared the infection by day 25. Retinoic acid treatment of A−mice at the peak of the infection eliminatedC. rodentiumwithin 16 days. Inflammation levels were not different between A+and A−mouse colons, although the A−mice were still infected at day 37. Increased mortality of A−mice was not due to systemic cytokine production, an inability to clear systemicC. rodentium, or increased pathogenicity. Instead, A−mice developed a severe gut infection with most of the A−mice surviving and resolving inflammation but not eliminating the infection. Improvements in vitamin A status might decrease susceptibility to enteric pathogens and prevent potential carriers from spreading infection to susceptible populations.