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Anti-inflammatory properties of the µ opioid receptor support its use

in the treatment of colon inflammation

Philippe1, t Dubuquoy1, Hervé Groux2, Valérie Brun2,

Myriam Tran Van Chuoï-t3, Gaveriaux-Ruff4, Jean-Frédéric

Colombel1, Brigitte L. Kieffer4 and Pierre Desreumaux1

1 Equipe Mixte INSERM 0114 sur la Physiopathologie des Maladies

Inflammatoires Intestinales, Centre Hospitalier Universitaire, Lille,

France

2 Unité INSERM U343, and TxCell, Hôpital de l'Archet 1, Nice, France

3 Unité INSERM U422, Centre Hospitalier Universitaire, Lille, France

4 Institut de Génétique et de Biologie Moléculaire et Cellulaire,

UMR7104, Strasbourg, France

Address correspondence to: Pierre Desreumaux, Service de

Gastroentérologie, Hôpital Huriez, Centre Hospitalier Universitaire,

Lille 59037, France. Phone: 33-3-20-44-5548; Fax: 33-3-20-44-4713; E-

mail: pdesreumaux@....

Received for publication August 26, 2002, and accepted in revised

form February 26, 2003.

The physiologic role of the µ opioid receptor (MOR) in gut

nociception, motility, and secretion is well established. To evaluate

whether MOR may also be involved in controlling gut inflammation, we

first showed that subcutaneous administration of selective peripheral

MOR agonists, named DALDA and DAMGO, significantly reduces

inflammation in two experimental models of colitis induced by

administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) or

peripheral expansion of CD4+ T cells in mice. This therapeutic effect

was almost completely abolished by concomitant administration of the

opioid antagonist naloxone. Evidence of a genetic role for MOR in the

control of gut inflammation was provided by showing that MOR-

deficient mice were highly susceptible to colon inflammation, with a

50% mortality rate occurring 3 days after TNBS administration. The

mechanistic basis of these observations suggests that the anti-

inflammatory effects of MOR in the colon are mediated through the

regulation of cytokine production and T cell proliferation, two

important immunologic events required for the development of colon

inflammation in mice and patients with inflammatory bowel disease

(IBD). These data provide evidence that MOR plays a role in the

control of gut inflammation and suggest that MOR agonists might be

new therapeutic molecules in IBD.

Related articles in JCI:

JCI 2003 111: 1263.