Interleukin-8 increases acetylcholine response of rat intestinal segments.
BACKGROUND
Interleukin-8 (IL-8) is a pro-inflammatory cytokine highly expressed in inflammatory bowel diseases, but whose effects on intestinal motility are unknown.


OBJECTIVE
To characterize the role of IL-8 in the contraction of rat intestinal segments.


METHODS
Contractile response to acetylcholine (ACh 10-6 M) in terminal ileal segments (including mucosa) from Wistar rats was measured before and after incubation (15, 30, 60 or 90 min) with IL-8 (1 ng/mL), and after 60 min of incubation with different doses of IL-8 (0, 0.1, 0.5, 1, 10 and 100 ng/mL). The effects of blocking neural transmission with tetrodotoxin (TTX) and inhibiting protein synthesis (cycloheximide) were tested. The contractile response of longitudinal muscle-myenteric plexus preparations (i.e. without mucosa) was measured after 60 min of incubation with 0.1 and 1 ng/mL of IL-8.


RESULTS
IL-8 increased ileal contraction induced by ACh 10(-6) M. This augmentation was significant after 60 min of incubation (58%, P=0.01) and persisted after 90 min (18%, P=0.04). A 60-min incubation period showed a dose-related effect, beginning at 0.5 ng/mL (30%, P=0.003) and reaching a peak at 1 ng/mL (58%, P=0.01). The same effect was also observed on colonic segments. TTX did not affect the IL-8 increase of ACh-induced contractions, which was completely abolished by cycloheximide. IL-8 had no significant effect on longitudinal muscle-myenteric plexus preparations.


CONCLUSIONS
In vitro, IL-8 increases contractile response of the ileum to ACh in a dose-dependent manner. This effect is not neurally mediated, but seems to involve protein synthesis by intestinal mucosa.
Plattner
V
V
Human Nutrition Research Center, INSERM U 539, Hôtel-Dieu, Nantes, France.
Leray
V
V
Leclair
M D
MD
Aubé
A C
AC
Cherbut
C
C
Galmiche
J P
JP
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology; D016209:Interleukin-8 / Q000008:administration & dosage / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D016209:Interleukin-8; D011500:Protein Synthesis Inhibitors; D014665:Vasodilator Agents; D013779:Tetrodotoxin; D003513:Cycloheximide; D000109:Acetylcholine