Background/aims: The possibility that interleukin-1 beta (IL-1beta) is a neuromodulator of the non-adrenergic non-cholinergic (NANC) inhibitory nerves which may be mediated by nitric oxide (NO) was recently reported from animal experiments. To clarify the physiological significance of the relationship between IL-1beta and NO in the normal human colon, enteric nervous responses to IL-1beta in the normal colon muscle strips were investigated.

Methodology: Normal colon muscle strips derived from patients who underwent colon resection for left-sided colon cancers (14 cases) were used. The subjects consisted of 8 men and 6 women, aged from 44 to 65 years with a mean age of 56.8 years. A mechanographic technique was used to evaluate in vitro colon muscle responses to IL-1beta of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers and N(G)-nitro-L-arginine (L-NNA).

Results: IL-1beta concentration dependently caused a relaxation reaction before and after the blockade of the adrenergic and cholinergic nerves. The frequency of relaxation responses after blocking the adrenergic and cholinergic nerves was higher than that before blocking, but there was no significant difference between them. Both tetrodotoxin and L-NNA inhibited the relaxation reaction in response to IL-1beta in the human colon.

Conclusions: These findings suggest that IL-1beta plays an important role in regulating relaxation of the normal human colon via nitregic nerves, and that NO plays a role as a neurotransmitter in the NANC inhibitory nerves.

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