zithromax and Inflammatory-Bowel-Diseases

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Rheumatoid; Autoimmune Diseases; Azithromycin; Biological Products; COVID-19; COVID-19 Drug Treatment; Enzyme Inhibitors; Female; Glucocorticoids; Hospitalization; Humans; Hydroxychloroquine; Immunomodulation; Immunosuppressive Agents; Inflammatory Bowel Diseases; Intensive Care Units; Janus Kinase Inhibitors; Male; Middle Aged; Respiration, Artificial; Sarcoidosis; SARS-CoV-2; Surveys and Questionnaires; Tumor Necrosis Factor Inhibitors; Young Adult

SARS-CoV-2 infection is a major concern and a new threat to immunocompromised patients. Patients with chronic inflammatory bowel diseases (IBDs) are at increased risk of infections, in particular when they have active disease and are on immunosuppressive treatment. The purpose of this study was to assess the clinical, biological and radiological features of three patients with COVID-19 associated with chronic IBD as well as their management and outcomes. The study was conducted at the Hassan II University Teaching Hospital in Fes, Morocco over a 3-month period. We assessed all patients with disease onset. All patients had mild symptoms or were asymptomatic. No changes or delays in treatment regimens occurred and none of patients developed severe COVID-19. Reverse transcription polymerase chain reaction (RT-PCR) test results were positive in all patients. Radiological examinations were conducted. Chest scanner showed ground-glass opacities in one case. Treatment was based on hydroxychloroquine with azithromycin. Outcome was good in all cases. This preliminary report suggests that patients with chronic IBD aren't at higher risk of developing COVID-19 compared to the general population.

Topics: Adult; Azithromycin; COVID-19; COVID-19 Drug Treatment; Female; Hospitals, University; Humans; Hydroxychloroquine; Immunosuppressive Agents; Inflammatory Bowel Diseases; Male; Middle Aged; Morocco

Inflammation-driven immune dysfunction supports the development of several chronic human disorders including inflammatory bowel diseases and rheumatoid arthritis. Macrolides are effective antibiotics endowed with immunomodulatory effects. In this study we report the chemical synthesis and the pharmacological characterization of CSY0073, a non-antibiotic derivative of azithromycin. CSY0073 was tested for efficacy in two experimental models of colitis induced by administering mice with dextran sulfate (DSS) and trinitrobenzene sulphonic acid (TNBS) and in collagen induced arthritis. Like azithromycin, CSY0073 improved clinical, macroscopic and histopathological scores in mice administered DSS (12.5μmol/kg/day p.o.) and TNBS (45μmol/kg/day p.o.). When administered to TNBS-treated mice, CSY0073 effectively attenuated influx of neutrophils and macrophages into the colonic mucosa and reduced the intestinal expression pro-inflammatory cytokines TNFα, IL-2 and IFNγ. CSY0073 (0.1 to 10μM) counter-regulated TNFα, IFNγ, IL-12 and IL-23 release caused by exposure of mouse spleen monocytes and CD11b+ cells isolated from the colonic lamina propria to endotoxin. CSY0073 (25μmol/kg/day) reduced clinical scores in the collagen induced murine model of rheumatoid arthritis. In myeloid cells, CSY0073 (10μM) prevented the nuclear translocation of the p65 subunit of NF-κB and its binding to canonical NF-κB responsive elements. In summary, we report a novel class of non-antibiotic 14-member macrocycles with anti-inflammatory and immune-modulatory effects. CSY0073, the prototype of this new class of macrolides exerts counter-regulatory activity on NF-κB signaling. This study suggests the exploitation of non-antibiotic macrolides in the treatment of inflammatory disorders characterized by immune dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Azithromycin; CD11b Antigen; Colitis; Collagen; Dextran Sulfate; Disease Models, Animal; Drug Discovery; Female; Humans; Immunologic Factors; Inflammation; Inflammatory Bowel Diseases; Male; Mice; Mucous Membrane; NF-kappa B; Signal Transduction; Trinitrobenzenesulfonic Acid