BACKGROUND/AIMS: Interleukin 1 beta (IL-1 beta) is known to regulate intestinal ion and water transport in vitro through prostaglandin release. This study investigated the effect of IL-1 beta on colonic net water flux in vivo to determine its nature (nerve mediation versus action on the epithelium), the mediators involved, and its relationship with mast cell degranulation. METHODS: Isolated colonic loops of anesthetized animals were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent collected at 15-minute intervals. Histological analysis was used to identify intact mast cells in colonic sections and radioimmunoassay to determine histamine levels. RESULTS: Both IL-1 beta and the calcium ionophore A23187 induced colonic hypersecretion during 30 minutes. This effect was blocked by tetrodotoxin, doxantrazole, and indomethacin but not chlorpheniramine. Recombinant human interleukin 1 beta decreased the number of intact mast cells. This effect was eliminated by doxantrazole but not tetrodotoxin or indomethacin. A23187 or IL-1 beta increased histamine levels in the effluent during 75 and 45 minutes, respectively. CONCLUSIONS: In vivo, rhL-1 beta induces colonic hypersecretion in rats. This effect is nerve mediated but not H1 receptor mediated and involves mast cell degranulation and prostaglandin release.
BACKGROUND/AIMS: Interleukin 1 beta (IL-1 beta) is known to regulate intestinal ion and water transport in vitro through prostaglandin release. This study investigated the effect of IL-1 beta on colonic net water flux in vivo to determine its nature (nerve mediation versus action on the epithelium), the mediators involved, and its relationship with mast cell degranulation. METHODS: Isolated colonic loops of anesthetized animals were infused with Ringer's buffer containing [14C]polyethylene glycol 4000. Net water flux was calculated according to 14C activity determined in the effluent collected at 15-minute intervals. Histological analysis was used to identify intact mast cells in colonic sections and radioimmunoassay to determine histamine levels. RESULTS: Both IL-1 beta and the calcium ionophore A23187 induced colonic hypersecretion during 30 minutes. This effect was blocked by tetrodotoxin, doxantrazole, and indomethacin but not chlorpheniramine. Recombinant humaninterleukin 1 beta decreased the number of intact mast cells. This effect was eliminated by doxantrazole but not tetrodotoxin or indomethacin. A23187 or IL-1 beta increased histamine levels in the effluent during 75 and 45 minutes, respectively. CONCLUSIONS: In vivo, rhL-1 beta induces colonic hypersecretion in rats. This effect is nerve mediated but not H1 receptor mediated and involves mast cell degranulation and prostaglandin release.