RESUMO
BACKGROUND: Inflammation is a crucial driver of host damage in patients with Clostridioides difficile colitis. We examined the potential for the intestinal microbiome to modify inflammation in patients with C. difficile colitis via the effects of gut-derived endotoxin on cytokine production. METHODS: Endotoxin from Escherichia coli and Pseudomonas aeruginosa as well as stool-derived endotoxin were tested for their ability to enhance interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) production by toxin B-stimulated peripheral blood mononuclear cells. Inflammasome and Toll-like receptor 4 (TLR4) blocking studies were done to discern the importance of these pathways, while metagenomic studies were done to characterize predominant organisms from stool samples. RESULTS: Endotoxin significantly enhanced the ability of C. difficile toxin B to promote IL-1ß production but not TNF-α. The magnitude of this effect varied by endotoxin type and was dependent on combined inflammasome and TLR4 activation. Stool-derived endotoxin exhibited a similar synergistic effect on IL-1ß production with less synergy observed for stools that contained a high proportion of γ-proteobacteria. CONCLUSIONS: The ability of endotoxin to enhance IL-1ß production highlights a manner by which the microbiome can modify inflammation and severity of C. difficile disease. This information may be useful in devising new therapies for severe C. difficile colitis.
Assuntos
Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Clostridioides difficile/imunologia , Endotoxinas , Fezes/microbiologia , Microbioma Gastrointestinal , Mediadores da Inflamação/metabolismo , Interleucina-1beta/sangue , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Criança , Pré-Escolar , Clostridioides difficile/genética , Colite , Feminino , Humanos , Inflamassomos/sangue , Inflamação , Interleucina-1beta/metabolismo , Leucócitos Mononucleares , Masculino , Receptor 4 Toll-Like/sangueRESUMO
There are many microvascular and macrovascular complications regarding uncontrolled diabetes mellitus (DM). Among them, diabetes myonecrosis is one of the complications but rarely seen in the uncontrolled DM patient population. Here, we present a rare case of DM myonecrosis in a patient with elevated hemoglobin A1c (HbA1c) of 18.2% and discuss the literature review of diabetes myonecrosis. A 48-year-old male with hypertension and uncontrolled type 2 diabetes mellitus (T2DM) with hemoglobin A1c of 18.2% presented with progressive swelling and pain in the right thigh for two days. Physical examination demonstrated swollen and tense tender right thigh with a circumference five inches larger than the left. Computed tomography (CT) and magnetic resonance imaging (MRI) results revealed severe myositis of the right leg, likely myonecrosis, and associated fascial edema/fasciitis. The patient was also complicated with diffuse anasarca, which was corrected with albumin transfusion and furosemide. Aspirin and lisinopril were also started for antithrombotic and cardioprotective effects. The right thigh swelling improved, and the patient could ambulate with supportive measures and regular physical therapy (PT). He was discharged home after 45 days of hospitalization. Diabetic myonecrosis is a rare condition and hence is underdiagnosed. In patients with uncontrolled diabetes, especially with diabetic complications, physicians should have high clinical suspicion to diagnose diabetic myonecrosis when patients present with an acute unilateral painful swollen limb. Our case highlights the complicated course of diabetes myonecrosis with anasarca, improved with supportive measures.