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Interleukin-1: effects on rabbit ileal mucosal ion transport in vitro
D C Chiossone1, P L Simon, P L Smith
1Department of Drug Delivery, Smith Kline and French Laboratories, King of Prussia, PA 19406-0939.
Insights
Recombinant human interleukin-1 (IL-1) inhibits sodium (Na+) and chloride (Cl-) absorption in rabbit ileum. This immune mediator affects electrical properties and ion transport, impacting intestinal function.
Area of Science:
- Gastroenterology
- Immunology
- Physiology
Background:
- Interleukin-1 (IL-1) is a key immune mediator.
- Intestinal ion transport is crucial for fluid balance.
Purpose of the Study:
- To investigate the effects of IL-1 on electrical properties and ion transport in rabbit ileum.
- To elucidate the mechanisms underlying IL-1's action on intestinal absorption.
Main Methods:
- In vitro Ussing chamber technique applied to rabbit ileum.
- Measurement of short-circuit current (Isc) and unidirectional fluxes of Na+ and Cl-.
- Pharmacological interventions including receptor antagonists and ion removal.
Main Results:
- Serosal IL-1 increased Isc in a concentration-dependent manner.
- IL-1 significantly reduced Na+ and Cl- absorption.
- The effects of IL-1 were independent of cholinergic, neuronal, and histaminergic pathways but sensitive to chloride availability and cyclooxygenase inhibitors.
Conclusions:
- Recombinant human IL-1 inhibits Na+ and Cl- absorption in rabbit ileum.
- IL-1's action on intestinal ion transport involves pathways sensitive to prostaglandins but not classical neurotransmitters.
Abstract:
Effects of recombinant human interleukin-1 (IL-1) on electrical properties and unidirectional fluxes of Na+ and Cl- in rabbit ileum were examined in vitro employing the Ussing chamber technique. Serosal but not mucosal addition of Il-1 increased short-circuit current (Isc) in a concentration-dependent manner with a maximal effect occurring at 5 ng/ml and a half-maximal effect at 0.9 ng/ml. The time required for a maximal effect was between 30 and 40 min. Flux measurements revealed that serosal IL-1 reduced Na+ and Cl- absorption. The increase in Isc elicited by IL-1 was not altered by pretreatment of tissues with serosal atropine, tetrodotoxin, the H1-histamine receptor antagonist, mepyramine or removal of Ca2+ from the serosal bathing solution. The effects of IL-1 were inhibited by removal of Cl- from the bathing solutions, or by indomethacin or piroxicam. Levels of immunoreactive thromboxane B2 and 6-keto-PGF1 alpha and PGE2 were not significantly altered by IL-1. These results demonstrate that IL-1 can inhibit Na+ and Cl- absorption in rabbit ileum.