The role of eosinophils and neutrophils in inflammation

The eosinophil is well recognized as a central effector cell in the inflame d asthmatic airway. Eosinophils release toxic basic proteins and lipid medi ators such as cysteinyl-leukotrienes that cause bronchial epithelial damage and airflow obstruction. Eosinophil-selective cytokines and chemokines inc luding interleukin (IL)-5, eotaxin and RANTES may represent targets for nov el asthma therapies. In contrast, the role of the neutrophil in asthma rema ins relatively obscure. Recent evidence from the ENFUMOSA project and elsew here suggests that neutrophils not only contribute to acute asthma exacerba tions, but also are present in high numbers in the airways of patients with chronic severe asthma. production by neutrophils of lipid mediators, react ive oxygen intermediates (ROI) and proteases such as elastase, may contribu te to airflow obstruction, epithelial damage and remodelling. Leukotriene B -4 and cytokines such as IL-8, granulocyte-macrophage colony stimulating fa ctor (GM-CSF), and tumour necrosis factor (TNF)alpha chemoattract neutrophi ls and reduce neutrophil apoptosis, and selective agents directed against t hese may prevent neutrophil influx and accumulation. Airway neutrophilia re mains apparent in severe asthma patients even after treatment with high dos es of corticosteroids. In vitro, corticosteroids paradoxically enhance neut rophil survival by reducing apoptosis, so corticosteroid therapy may exacer bate neutrophil activity in vivo. Both corticosteroids and cytokines may su ppress neutrophil apoptosis by upregulating endogenous synthesis of leukotr iene (LT)B-4. Specific blockade of LTB4 synthesis or LTB4, receptors may in duce neutrophil apoptosis and combat the unwanted effects of high-dose ster oids on neutrophil survival. Phagocytosis of apoptotic neutrophils stimulat es important signals that down-regulate pro-inflammatory cytokine productio n by macrophages, allowing resolution and repair processes to prevail.