FECAL TUMOR-NECROSIS-FACTOR-ALPHA IN INDIVIDUALS WITH HIV-RELATED DIARRHEA

Objective: HIV-related gastrointestinal infection is associated with d iarrhoea, weight loss, mucosal inflammation and increased intestinal p ermeability. As tumour necrosis factor (TNF)-alpha may mediate these f eatures this cytokine was measured in the faeces of HIV-seropositive i ndividuals with diarrhoea to assess its role in the pathogenesis of HI V-related gastrointestinal disease and the association with specific i ntestinal pathogens. Design: Prospective study. Methods: Two hundred a nd four HIV-seropositive individuals provided stool samples that were analysed for faecal TNF-alpha (FTNF-alpha) using a standard sandwich e nzyme-linked immunosorbent assay. Results: Stool from patients with ba cterial, cytomegalovirus (CMV) and microsporidial diarrhoea had signif icantly elevated FTNF-alpha compared with those who had pathogen-negat ive diarrhoea (P<0.05). FTNF-alpha was not raised in cryptosporidiosis , pathogen-negative or solid stool. In subjects with diarrhoea of more than 2 weeks duration and three stool samples negative For enteric pa thogens, FTNF-alpha greater than 15 U/ml has a sensitivity of 88% and a specificity of 66% for the diagnosis of diarrhoea-related CMV enteri tis. Conclusion: TNF-alpha production may have a role in the pathogene sis of bacterial, microsporidial and CMV-related diarrhoea in HIV-sero positive individuals. Thus, anti-TNF-alpha agents may have a therapeut ic role in the management of these conditions. FTNF-alpha greater than 15 U/ml in apparently pathogen-negative diarrhoea may suggest endosco pic gastrointestinal biopsy to diagnose CMV enteritis.