Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-α, interferon-γ, interleukin-1β (IL-1β), and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-β are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an important physiological and pathological effect on intestinal tight junction (TJ) barrier. Consistent with their known pro-inflammatory activities, pro-inflammatory cytokines cause a disturbance in intestinal TJ barrier, allowing increased tissue penetration of luminal antigens. Recent studies indicate that the inhibition of cytokine induced increase in intestinal TJ permeability has an important protective effect against intestinal mucosal damage and development of intestinal inflammation. In this review, the effects of various pro-inflammatory and anti-inflammatory cytokines on intestinal TJ barrier and the progress into the mechanisms that mediate the cytokine modulation of intestinal TJ barrier are reviewed.

Background: Care homes are experiencing large outbreaks of COVID-19 associated with high case-fatality rates. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020. Methods: Residents and staff had nasal swabs for SARS CoV-2 testing using RT-PCR and were followed-up for 14 days. They were categorized as symptomatic, post-symptomatic or pre-symptomatic if they had symptoms at the time of testing, in the two weeks before or two weeks after testing, respectively, or asymptomatic throughout. Virus isolation and whole genome sequencing (WGS) was also performed. Findings: Across the six care homes, 105/264 (39.8%) residents were SARS CoV-2 positive, including 28 (26.7%) symptomatic, 10 (9.5%) post-symptomatic, 21 (20.0%) pre-symptomatic and 46 (43.8%) who remained asymptomatic. Case-fatality at 14-day follow-up was highest among symptomatic SARS-CoV-2 positive residents (10/28, 35.7%) compared to asymptomatic (2/46, 4.3%), post-symptomatic (2/10, 20.0%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 53/254 (20.9%) were SARS-CoV-2 positive and 26/53 (49.1%) remained asymptomatic. RT-PCR cycle-thresholds and live-virus recovery were similar between symptomatic/asymptomatic residents/staff. Higher RT-PCR cycle threshold values (lower virus load) samples were associated with exponentially decreasing ability to recover infectious virus (P<0.001). WGS identified multiple (up to 9) separate introductions of different SARS-CoV-2 strains into individual care homes. Interpretation: A high prevalence of SARS-CoV-2 positivity was found in care homes residents and staff, half of whom were asymptomatic and potential reservoirs for ongoing transmission. A third of symptomatic SARS-CoV-2 residents died within 14 days. Symptom-based screening alone is not sufficient for outbreak control.

Background: Care homes have been disproportionately affected by the COVID-19 pandemic and continue to suffer lar ge outbreaks even when community infection rates are declining, thus representing important pockets of transmission. We assessed occupational risk factors for SARS-CoV-2 infection among staff in six care homes experiencing a COVID-19 outbreak during the peak of the pandemic in London, England. Methods: Care home staff were tested for SARS-COV-2 infection by RT-PCR and asked to report any symptoms, their contact with residents and if they worked in different care homes. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Results: In total, 53 (21%) of 254 staff were SARS-CoV-2 positive but only 12/53 (23%) were symptomatic. Among staff working in a single care home, SARS-CoV-2 positivity was 15% (2/13), 16% (7/45) and 18% (30/169) in those reporting no, occasional and regular contact with residents. In contrast, staff working across different care homes (14/27, 52%) had a 3.0-fold (95% CI, 1.9-4.8; P < 0.001) higher risk of SARS-CoV-2 positivity than staff working in single care homes (39/227, 17%). WGS identified SARS-CoV-2 clusters involving staff only, including some that included staff working across different care homes. Conclusions: SARS-CoV-2 positivity was significantly higher among staff working across different care homes than those who were working in the same care home. We found local clusters of SARS-CoV-2 infection between staff only, including those with minimal resident contact. Infection control should be extended for all contact, including those between staff, whilst on care home premises.

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The cellular and molecular regulation of intestinal absorption of the water-soluble vitamin riboflavine (RF) is poorly understood. The availability of a suitable in vitro cultured system that possesses the transport characteristics of the native intestinal absorptive cells would provide a powerful means to address this issue. In this study, we examined RF uptake by the human-derived cultured Caco-2 intestinal epithelial cells. RF uptake was Na+ and pH independent and occurred without metabolic alterations of the transported RF. Initial rate of RF uptake was temperature dependent and saturable as a function of concentration at 37 degrees C but not at 4 degrees C (apparent Michaelis constant = 0.30 +/- 0.03 microM, maximal velocity = 209.90 +/- 24.40 pmol.mg protein-1.3 min-1). Unlabeled RF, lumiflavine, 8-amino-riboflavine, isoriboflavine, and lumichrome in the incubation solution caused significant inhibition of RF uptake. RF uptake was also energy dependent and was sensitive to the inhibitory effect of sulfhydryl group reagents. The membrane transport inhibitor amiloride, but not 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 4-acetamide-4'-isothiocyanostilbene-2,2'-disulfonic acid, furosemide, or probenecid, inhibited RF uptake in a competitive (inhibitory constant = 0.48 mM) and reversible manner. Growing Caco-2 monolayers in a RF-deficient and oversupplemented media caused significant up- and downregulation of RF uptake, respectively. These results demonstrate the existence of a carrier-mediated system for RF uptake by Caco-2 cells and provide new information regarding amiloride sensitivity, involvement of sulfhydryl groups, and up- and downregulation by the substrate level and clarify the controversy regarding the role of Na+ in the uptake process.(ABSTRACT TRUNCATED AT 250 WORDS)