Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: an in vitro study

• Published in: European journal of clinical investigation Vol. 33; no. 8; pp. 704 - 712
• Main Authors: Natale, L., Piepoli, A. L., De Salvia, M. A., De Salvatore, G., Mitolo, C. I., Marzullo, A., Portincasa, P., Moschetta, A., Palasciano, G., Mitolo-Chieppa, D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-08-2003
• Subjects: Animals; Carbachol - pharmacology; Cholinergic Agents - pharmacology; Colitis; Colon - drug effects; Colon - pathology; Colon - physiology; cytokines; Electrophysiology; Gastrointestinal Motility - drug effects; Gastrointestinal Motility - physiology; inflammatory bowel disease; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Intestinal Mucosa - physiology; Male; Miotics - pharmacology; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; Neural Conduction - drug effects; Neural Conduction - physiology; Neurotransmitter Agents - pharmacology; Rats; Rats, Sprague-Dawley; smooth muscle contractility; Tachykinins - pharmacology
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.1365-2362.2003.01200.x

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.
Materials and method 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%).
Conclusion 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.