Alternatively, deleterious increases in pro-inflammatory mediators other than IL-8 and other effects of E2 (such as inhibition of aspects of innate immunity or mucociliary clearance) may more substantially aggravate CF lung disease over time than any benefit from reduction caused by E2 in IL-8 from airway epithelial cells during acute exacerbations, and thus E2 could make a net pro-inflammatory contribution to the cause of the CF gender gap. The gene discussed is CXCL8; the disease is lung disorder.