ABSTRACT
As one of the most important endogenous chemotactic factors for neutrophils, the chemokine CXCL8 (IL-8) is involved in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by massive neutrophil infiltration in the lung. Since neutralization of CXCL8 with polyclonal antibody has been shown to reduce the severity of ALI/ARDS in animal models, we explored the potential of humanized anti-CXCL8 antibody as a preventive or therapeutic agent for ALI. We used a 'two-hit' protocol to induce ALI in rabbits that showed extensive edema in the alveolar lumina, marked infiltration of neutrophils in the lung tissue, fibrin deposition in alveolar space, and destruction of pulmonary architecture, culminating in severe hypoxemia. Concomitant challenge with endotoxin after priming with oleic acid (OA) induced a marked elevation of CXCL8 level in bronchoalveolar lavage fluid. Treatment of the rabbits with a humanized anti-CXCL8 antibody prevented neutrophil infiltration in the lung in association with alleviated ALI syndrome. Our results indicate a promising future for utilization of humanized anti-CXCL8 antibody in the prevention and treatment of ALI and ARDS in human.
Subject(s)
Acute Lung Injury/therapy , Antibodies, Monoclonal/therapeutic use , Interleukin-8/antagonists & inhibitors , Respiratory Distress Syndrome/therapy , Acute Lung Injury/prevention & control , Animals , Bronchoalveolar Lavage , Capillary Permeability/immunology , Edema/immunology , Endotoxins/immunology , Female , Fibrin/immunology , Hypoxia/immunology , Interleukin-1/chemistry , Interleukin-1/immunology , Interleukin-8/immunology , Lung/pathology , Male , Mice , Neutrophils/immunology , Oleic Acid/immunology , Rabbits , Respiratory Distress Syndrome/prevention & control , Tumor Necrosis Factor-alpha/chemistry , Tumor Necrosis Factor-alpha/immunologyABSTRACT
BACKGROUND: Interleukin-8 (IL-8) is a member of the CXC chemokine family, which involved in tumor growth, metastasis and angiogenesis. The aim of this study is to investigate the expression of IL-8 in non-small cell lung cancer (NSCLC) and its clinicopathologic significance. METHODS: The expression of IL-8 protein and the intratumoral microvessel density (MVD) were detected in 114 cases of NSCLC on tissue array by immunohistochemical method (EnVisionTM method). RESULTS: The positive rate of IL-8 expression was 81.6% (93/114) in 114 cases of the primary lung cancer and 79.1% (34/43) in metastatic lymph nodes respectively. And it was remarkably higher in NSCLC with lymph node metastasis (93.0%, 40/43)) than in those without lymph node metastasis (74.6%, 53/71) (P < 0.05). IL-8 protein expression in primary lung cancer tissues was positively related to TNM stages (P < 0.05), but not to histological type, differentiation degree, age and sex of patients (P > 0.05). In addition, there was significant difference in MVD between IL-8 positive NSCLC tissues (22.1±13.6) and negative ones (14.8±11.2) (P < 0.05). CONCLUSIONS: The present study suggests that there is overexpression of IL-8 in NSCLC, which is closely related to angiogenesis, TNM stages and lymph node metastasis. Detection of IL-8 protein may be helpful to evaluate biological characteristics and therapy for NSCLC.
