Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD).
Activation of nuclear factor kappa B (NFkappaB), which is involved in their gene transcription,
is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial
in treating colonic inflammation, we investigated if butyrate promotes this effect
by acting on proinflammatory cytokine expression.
Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral
blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment
of secretion of tumour necrosis factor (TNF) and mRNA levels. NFkappaB p65 activation
was determined by immunofluorescence and gene reporter experiments. Levels of NFkappaB
inhibitory protein (IkappaBalpha) were analysed by western blotting. The in vivo efficacy
of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced
Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by
intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide
(LPS) induced expression of cytokines by PBMC and transmigration of NFkappaB from
the cytoplasm to the nucleus. LPS induced NFkappaB transcriptional activity was decreased
by butyrate while IkappaBalpha levels were stable. Butyrate treatment also improved
TNBS induced colitis.
Butyrate decreases proinflammatory cytokine expression via inhibition of NFkappaB
activation and IkappaBalpha degradation. These anti-inflammatory properties provide
a rationale for assessing butyrate in the treatment of CD.