Elevated Tear Fluid Levels of MIP-1α in Patients with Cystic Fibrosis

Abstract

Cystic fibrosis (CF) is the commonest multisystem genetic disease of white races, caused by mutations in the cystic fibrosis transmembrane regulator (CFTR), encoded on the long arm of chromosome 7. Mutations in the CFTR gene result in defective sodium, chloride, and water transport in the epithelial cells of the respiratory, hepatobiliary, gastrointestinal, and reproductive tracts, the pancreas, and the eye. The pathogenesis of ocular changes in CF is still unknown, but CF belongs to the large pathologic group of ocular surface epithelial diseases, termed keratoconjunctivitis sicca (KCS), that develop in dry eye syndrome. The aim of this study was to evaluate the levels of macrophage inflammatory protein-1alpha (MIP-1alpha) in the tear fluid of CF patients. We also investigated the correlation between the tear levels of this chemokine and clinical severity of CF and ocular surface disease. We studied 25 patients with CF with a mean age of 14 years. Chemokine levels were determined by ELISA. Complete ophthalmic examination, including dry eye tests, were used to study the ocular surface. The tear levels of MIP-1alpha in the CF patients were significantly higher when compared with healthy controls. We found a negative correlation between the tear levels of MIP-1alpha and clinical severity in CF patients and a positive correlation between the tear levels of MIP-1alpha and the presence of dry eye findings in CF patients. This current study indicates that chemokines play an important role in the ongoing inflammatory response. Our findings may help to explain one of the key factors contributing to the pathogenesis of ocular surface changes in CF patients.

Neonatal hyperoxia alters the host response to influenza A virus infection in adult mice through multiple pathways

“…Given the potential for chemokine redundancy in our model, it is possible that other monocyte chemoattractants could be compensating for the lack of MCP-1 gene expression and contributing to the observed fibrosis in infected mice exposed to hyperoxia at birth. For example, increased levels of the monocyte chemoattractant protein MIP-1␣ have been observed in patients with cystic fibrosis and in a mouse model of bleomycin-induced pulmonary fibrosis (31,37). However, we have previously shown that levels of MIP-1␣ in BAL fluid collected from infected adult mice exposed to hyperoxia at birth were not different from levels in infected siblings birthed into room air during any of the postinfection time points examined in the study (33).…”

Alveolar macrophages and CC chemokines are increased in children with cystic fibrosis

“…MCP-1 (CCL2) and MIP-3a (CCL20) have both been reported to be elevated in BALF in subjects with CF [12,25] and in induced sputum and blood (CCL2) [23] compared with controls. MIP-1a (CCL3) has also been identified as being elevated in the tears of subjects with CF compared with healthy controls [26].…”

Practical issues concerning tear protein assays in dry eye

“…The tear chemokines which have been implicated in dry eye are CX3CL1 [ 64 ], CXCL10 [ 64 ], CCL4/MIP-1beta [ 124 ],[ 125 ], CCL3/MIP-1alpha [ 57 ],[ 125 ],[ 126 ], CCL5/RANTES [ 57 ], CXCL9, -10, and -11 [ 127 ]. The tear levels of CXCL9, -10 and -11 were 1,148 +/- 1,088, 24,338 +/- 8,706, and 853 +/- 334 pg/mL, in dry eye, and only 272 +/- 269, 18,149 +/- 5,266, and 486 +/- 175 pg/mL in controls respectively [ 41 ].…”