The role of eosinophils and neutrophils in inflammation

Clin Exp Allergy. 2000 Jun:30 Suppl 1:22-7. doi: 10.1046/j.1365-2222.2000.00092.x.

Abstract

The eosinophil is well recognized as a central effector cell in the inflamed asthmatic airway. Eosinophils release toxic basic proteins and lipid mediators such as cysteinyl-leukotrienes that cause bronchial epithelial damage and airflow obstruction. Eosinophil-selective cytokines and chemokines including interleukin (IL)-5, eotaxin and RANTES may represent targets for novel asthma therapies. In contrast, the role of the neutrophil in asthma remains relatively obscure. Recent evidence from the ENFUMOSA project and elsewhere suggests that neutrophils not only contribute to acute asthma exacerbations, but also are present in high numbers in the airways of patients with chronic severe asthma. Production by neutrophils of lipid mediators, reactive oxygen intermediates (ROI) and proteases such as elastase, may contribute to airflow obstruction, epithelial damage and remodelling. Leukotriene B4 and cytokines such as IL-8, granulocyte-macrophage colony stimulating factor (GM-CSF), and tumour necrosis factor (TNF)alpha chemoattract neutrophils and reduce neutrophil apoptosis, and selective agents directed against these may prevent neutrophil influx and accumulation. Airway neutrophilia remains apparent in severe asthma patients even after treatment with high doses of corticosteroids. In vitro, corticosteroids paradoxically enhance neutrophil survival by reducing apoptosis, so corticosteroid therapy may exacerbate neutrophil activity in vivo. Both corticosteroids and cytokines may suppress neutrophil apoptosis by upregulating endogenous synthesis of leukotriene (LT)B4. Specific blockade of LTB4 synthesis or LTB4 receptors may induce neutrophil apoptosis and combat the unwanted effects of high-dose steroids on neutrophil survival. Phagocytosis of apoptotic neutrophils stimulates important signals that down-regulate pro-inflammatory cytokine production by macrophages, allowing resolution and repair processes to prevail.

Publication types

  • Review

MeSH terms

  • Asthma / physiopathology*
  • Eosinophils / physiology*
  • Humans
  • Inflammation / physiopathology*
  • Neutrophils / physiology*
  • Respiratory System