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

L. Natale; A. L. Piepoli; M. A. De Salvia; G. De Salvatore; C. I. Mitolo; A. Marzullo; P. Portincasa; A. Moschetta; G. Palasciano; D. Mitolo-Chieppa

doi:10.1046/j.1365-2362.2003.01200.x

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

L. Natale, A. L. Piepoli, M. A. De Salvia, G. De Salvatore, C. I. Mitolo, A. Marzullo, P. Portincasa, A. Moschetta, G. Palasciano, D. Mitolo-Chieppa

Pharmacology

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

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 E_max 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 E_max 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.

Original language	English (US)
Pages (from-to)	704-712
Number of pages	9
Journal	European Journal of Clinical Investigation
Volume	33
Issue number	8
DOIs	https://doi.org/10.1046/j.1365-2362.2003.01200.x
State	Published - Aug 1 2003

Keywords

Colitis
Cytokines
Inflammatory bowel disease
Smooth muscle contractility

ASJC Scopus subject areas

Biochemistry
Clinical Biochemistry

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10.1046/j.1365-2362.2003.01200.x

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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. (2003). Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: An in vitro study. European Journal of Clinical Investigation, 33(8), 704-712. https://doi.org/10.1046/j.1365-2362.2003.01200.x

Natale, L, Piepoli, AL, De Salvia, MA, De Salvatore, G, Mitolo, CI, Marzullo, A, Portincasa, P, Moschetta, A, Palasciano, G & Mitolo-Chieppa, D 2003, 'Interleukins 1 beta and 6 induce functional alteration of rat colonic motility: An in vitro study', European Journal of Clinical Investigation, vol. 33, no. 8, pp. 704-712. https://doi.org/10.1046/j.1365-2362.2003.01200.x

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abstract = "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.",

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T2 - An in vitro study

AU - Natale, L.

AU - Piepoli, A. L.

AU - De Salvia, M. A.

AU - De Salvatore, G.

AU - Mitolo, C. I.

AU - Marzullo, A.

AU - Portincasa, P.

AU - Moschetta, A.

AU - Palasciano, G.

AU - Mitolo-Chieppa, D.

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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.

AB - 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.

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KW - Cytokines

KW - Inflammatory bowel disease

KW - Smooth muscle contractility

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

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