Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response

MJ Leckie, A Brinke, J Khan, Z Diamant, BJ O'Connor, CM Walls, AK Mathur, HC Cowley, KF Chung, R Djukanovic, TT Hansel, ST Holgate, PJ Sterk and PJ Barnes

Lancet 2001, 356: 2144-2148

Topic: Respiratory immunology, Asthma

Readership: General interest

Reported by: Undurti Das

The electronic version of this article is the complete one and can be found online at: http://newdesign.respiratory-research.com/paperreports/rr-2001-68534

Report date:	18 September 2001
Published:	22 February 2001

Respiratory Research 2001, 2:68534

Keywords: Asthma, eosinophils, IL-5

Context

Allergic bronchial asthma is an inflammatory disease characterized by eosinophilia. This inflammatory response is believed to be due to an imbalance between Th1 and Th2 responses. Th1 cells produce predominantly interferon-? and interleukin (IL)-2, whereas Th2 cells produce IL-4, -5, -9 and -13. Increased production of IL-5 causes eosinophilia, whereas IL-4 and IL-13 enhance the production of IgE. In asthma, there is an increase in IL-5 production, and it is known that increased serum IL-5 is associated with a fall in the FEV₁ (forced expiratory volume in 1 s). Hence, it is logical to think that monoclonal antibody to IL-5 could be of benefit in asthma.

Significant findings

Although monoclonal antibody to IL-5 lowered the number of blood eosinophils for up to 16 weeks and the number of sputum eosinophils at 4 weeks, no significant change in the late asthmatic response or in airway hyperresponsiveness to histamine was noted. Hence, the authors suggested that eosinophils might not have a major role in the pathobiology of asthma.

Comments

The negative results of this study suggest the following: eosinophils might not be important mediators of asthma; several other cytokines might also be involved in the pathogenesis of asthma and, hence, neutralizing IL-5 alone is not adequate to inhibit the pathology of asthma; a combination of IL-12 and antibody to IL-5 might need to be given in asthma treatment to see a significant beneficial result. Had the levels of IgE been measured they might have provided some clue as to why the treatment did not work. It is possible that more frequent administration of antibody to IL-5 is necessary to prevent late asthmatic reaction.

Methods

Double-blind, randomized, placebo-controlled, human trial in mild asthma; intravenous infusion of humanized monoclonal antibodies; inhaled allergen challenge.

Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response

Context

Significant findings

Comments

Methods

Additional information

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