Tryptophan catabolites regulate mucosal sensitization to ovalbumin in respiratory airways.

Abstract

BACKGROUND:

Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in tryptophan catabolism, is important in generating tolerance at the foetal-maternal interface. Studies using 1-methyl-tryptophan (1-MT), the specific inhibitor of IDO, showed that this enzyme is important in interferon-gamma (IFN-gamma)-dependent inhibition of allergic inflammation in the respiratory airway during immunotherapy.

AIMS OF STUDY:

We investigated the role of IDO in the development of allergic sensitization, leading to allergic inflammation and airway hyper-responsiveness (AHR).

METHODS:

We used a mouse model to generate mucosal tolerance to lipopolysaccharide-free ovalbumin (OVA) following repeated intranasal inoculation of OVA over a 3-day period. We tested the successful induction of tolerance by subsequent intraperitoneal (i.p.) sensitization followed by intranasal challenge with OVA. A slow-release pellet of 1-MT implanted into mice was used to block IDO activity prior to repeated intranasal inoculation of OVA. We measured T-cell proliferation in response to OVA, determined airway inflammation, and measured AHR to intranasal methacholine to investigate the role of IDO in sensitization to OVA.

RESULTS:

Repeated intranasal administration of OVA generated tolerance and prevented a subsequent sensitization to OVA via the i.p. route. This response was inhibited in mice receiving a slow-release pellet of 1-MT. However, we successfully reconstituted tolerance in mice receiving 1-MT following intra-peritoneal injection of a mixture of kynurenine and hydroxyanthranilic acid.

CONCLUSION:

Our data suggest that, in addition to their role in IFN-gamma-mediated inhibition of allergic airway inflammation, products of tryptophan catabolism play an important role in the prevention of sensitization to potential allergens in the respiratory airway.

• Authors: S O Odemuyiwa, C Ebeling, V Duta, M Abel, L Puttagunta, O Cravetchi, C Majaesic, H Vliagoftis, R Moqbel
• Journal: Allergy (Allergy) Vol. 64 Issue 3 Pg. 488-92 (Mar 2009) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 18721245 (Publication Type: Journal Article)

Chemical References

• Allergens
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Interferon-gamma
• Tryptophan
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Immune Tolerance (physiology)
• Immunity, Mucosal (drug effects)
• Indoleamine-Pyrrole 2,3,-Dioxygenase (metabolism)
• Interferon-gamma (immunology)
• Lymphocyte Activation (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Ovalbumin (immunology)
• Respiratory Mucosa (drug effects, immunology, metabolism)
• T-Lymphocytes (immunology)
• Tryptophan (analogs & derivatives, metabolism)