Activated NF-κB (p65) colocalized with CD68+ macrophages in ICAs and also with MCP-1 and VCAM-1. Gene expression of MCP-1, VCAM-1, MMP-2, MMP-9, IL-1β, and iNOS along with reduced infiltration of CD68+ macrophages was observed in NF-κB p50 KO mice associated with decreased incidence of ICAs formation. Macrophage infiltration, expression of downstream genes, and ICAs formation were dramatically inhibited by NF-κB decoy ODN. Here, MMP9 is linked to familial isolated congenital asplenia.