Interleukin (IL)-4Induces Production Of The Lung Cytokine-induced Neutrophil Chemoattractants (CINCs) And Intercellular Adhesion Molecule (ICAM)-1in Rats

Purpose: To investigate the direct effect of IL-4on the inflammatory cells burden inbronchoalveolar lavage fluid (BALF) and lung, the cytokine-induced neutrophilchemoattractants (CINCs) and intercellular adhesion molecule (ICAM-1) levels in BALFsupernatant and the mRNA expression in lung tissue, comparing with the effect oflipopolysaccharide (LPS) on their expression.Method: Rats were divided into three groups:(1) dose dependent group: Recombinant ratIL (rrIL)-4(2,4or8ug/animal, Peprotech, UK; dissolved in200ul normal saline (NS))was intranasally instilled, and all rats were sacrificed6h later;(2) time dependent group:RrIL-4(4ug/animal, dissolved in200ul NS) was similarly instilled intranasally, and ratswere sacrificed after6h,12h and24h respectively;(3) asthmatic group: Asthmatic lunginflammation was induced; RrIL-4(4ug/animal, dissolved in200ul NS) or LPS(6mg/kg/animal, dissolved in200ul NS) was intranasally instilled after the last challengewith ovalbumin (OVA). Rats were sacrificed6hours later. The present study describes thatIL-4induced leukocyte profile in BALF and airway inflammation in rats usingWright-Gimesa and Haematoxylin-Eosin (HE) staining. The effects of CINC-1,-2α,-2βand-3and ICAM-1stimulated by IL-4in the normal and asthmatic rat lungs were studiedusing ELISA and real time PCR methods. Result: We demonstrated that the intranasal instillation of rrIL-4does not induce arecruitment of neutrophil in BALF in rats. However, intranasal instillation of rrIL-4increased the CINC-1protein level in BALF within6hours in a dose-dependent manner,but mRNA expression of CINC-1,-2α,-2β and-3were not promoted. Moreover, rrIL-4augmented the mRNA expression and protein level of ICAM-1within6hours. However,the increase in CINC-1and ICAM-1protein level in BALF was of the same magnitude inthe asthmatic rats treated with rrIL-4and asthmatic rats. LPS induced a recruitment ofneutrophil in BALF and lung in rats; LPS also increased the lung CINC-1,-2α,-3andICAM-1expression in rats.Conclution: These findings indicate that while IL-4does not directly promote therecruitment of neutrophils in the rat lungs, it may contribute to airway neutrophilia throughup-regulation of CINC-1and ICAM-1. Moreover, LPS induces airway neutrophilia bydirectly induce inflammatory cells, especial neutrophils to the rat lungs; LPS also increasedthe lung CINC-1,-2α,-3and ICAM-1expression in the rat lungs.