Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study.
BACKGROUND
In rodents, interleukins administration induces intestinal changes similar to those found in inflammatory bowel disease. We investigated the effects of in vivo subchronic treatment with IL-1 beta and IL-6 on rat colonic mucosa and circular smooth muscle.


METHODS
We evaluated transmucosal electrical parameters (Ussing chambers) and early changes of in vitro direct contractility induced by carbachol and tachykinins. Alterations in excitatory and inhibitory neurotransmission were studied with electrical field stimulation (EFS).


RESULTS
Treatment with interleukins induces inflammation proved by fever, early signs of colonic histological damage and changes in mucosal ion transport. Concentration response-curve to carbachol was significantly lower in treated rats (P<0.02) with significant difference in Emax between control (1.67+/-0.17 g) and treated preparations (1.20+/-0.13 g) (P<0.05). Concentration response-curve to NK2 agonist was significantly lower in the treated rats (P<0.005) with a significant difference in Emax between the control (0.26+/-0.04 g) and treated preparations (0.12+/-0.02 g) (P<0.02). None of the drugs used induces changes in EC50. The contractile reflex response to electrically induced distension was significantly higher in the treated rats and more reduced after administration of atropine. Adding NK2 receptor antagonist resulted in a further reduction being observed in the treated and control rats (P=NS). Relaxation by EFS on cholinergic tone was not different between treatments, although pretreatment with L-NNA resulted in greater relaxation in the treated (-21.7%) than in the control rats (-14.8%).


CONCLUSIONS
Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.
Natale
L
L
Dipartimento di Farmaclogia e Fisiologia Umana, Università degli Studi di Bari, Bari, Italy.
Piepoli
A L
AL
De Salvia
M A
MA
De Salvatore
G
G
Mitolo
C I
CI
Marzullo
A
A
Portincasa
P
P
Moschetta
A
A
Palasciano
G
G
Mitolo-Chieppa
D
D
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D004594:Electrophysiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D008916:Miotics / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins / Q000494:pharmacology
D018678:Cholinergic Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008916:Miotics; D018377:Neurotransmitter Agents; D015320:Tachykinins; D002217:Carbachol