Cysteinyl leukotriene-dependent interleukin-5 production leading to eosinophilia during late asthmatic response in guinea-pigs.

Abstract

BACKGROUND:

Allergic airway eosinophilia is suppressed by cysteinyl leukotriene (CysLT) receptor (CysLT1 receptor) antagonists in several species including humans and guinea-pigs, suggesting that CysLTs are directly or indirectly involved in induction of the response.

OBJECTIVE:

We examined the effect of CysLT antagonists (pranlukast and MCI-826) on antigen inhalation-induced eosinophilia in peripheral blood and lung, and on IL-5 activity in serum during late increase of airway resistance (late asthmatic response, LAR) in sensitized guinea-pigs.

METHODS:

Guinea-pigs inhaled ovalbumin (OVA) + Al(OH)3 and OVA mists alternately for sensitization and challenge, respectively, once every 2 weeks. At the fifth challenge, the effects of CysLT antagonists and an anti-IL-5 antibody (TRFK-5) on the occurrence of LAR, and blood and lung eosinophilia, which appeared at 5 h after challenge, were examined. The time-course of IL-5 activity in the serum after the challenge was evaluated by measuring in vitro 'eosinophil survival prolongation activity'. The influence of CysLT antagonists on IL-5 activity was assessed.

RESULTS:

CysLT antagonists and TRFK-5 completely abolished blood and lung eosinophilia. LAR was suppressed by both MCI-826 and TRFK-5 by 40-50%. Sera obtained from sensitized, challenged animals 3 h and 4 h after challenge induced an obvious prolongation of eosinophil survival. The activity of the sera was completely neutralized by prior exposure to TRFK-5, suggesting that it reflected IL-5 activity. Increased IL-5 activity in the serum was inhibited by both pranlukast and MCI-826 by over 90%.

CONCLUSIONS:

CysLTs produced after antigen provocation sequentially induced IL-5 production from some immune component cells via CysLT1 receptor activation. Thus, it is likely that CysLTs indirectly cause antigen-induced eosinophilia through IL-5 production.

• Authors: T Nabe, K Yamashita, M Miura, T Kawai, S Kohno
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 32 Issue 4 Pg. 633-40 (Apr 2002) ISSN: 0954-7894 [Print] England
• PMID: 11972613 (Publication Type: Journal Article)

Chemical References

• Chromones
• Interleukin-5
• Leukotriene Antagonists
• Leukotrienes
• Membrane Proteins
• Receptors, Leukotriene
• Thiazoles
• cysteinyl-leukotriene
• MCI 826
• Ovalbumin
• cysteinyl leukotriene receptor 2
• Cysteine
• leukotriene D4 receptor
• pranlukast

Topics

• Animals
• Asthma (immunology)
• Cell Survival (drug effects)
• Chromones (pharmacology)
• Cysteine (physiology)
• Eosinophilia (blood)
• Guinea Pigs
• Interleukin-5 (antagonists & inhibitors, biosynthesis, physiology)
• Kinetics
• Leukotriene Antagonists (pharmacology)
• Leukotrienes (physiology)
• Male
• Membrane Proteins
• Ovalbumin (immunology)
• Pulmonary Eosinophilia (immunology)
• Receptors, Leukotriene
• Thiazoles (pharmacology)