Chlamydia trachomatis infection of the female genital tract can lead to irreversible fallopian tube scarring. In the mouse model of genital infection using Chlamydia muridarum, IL-1R signaling plays a critical role in oviduct tissue damage. In this study, we investigated the pathologic role of IL-1a, one of the two proinflammatory cytokines that bind to IL-1R. Il1a2/2 mice infected with C. muridarum cleared infection at their cervix at the same rate as wild-type (WT) mice, but were significantly protected from end point oviduct damage and fibrosis. The contribution of IL-1a to oviduct pathology was more dramatic than observed in mice deficient for IL-1b. Although chlamydial burden was similar in WT and Il1a2/2 oviduct during peak days of infection, levels of IL-1b, IL-6, CSF3, and CXCL2 were reduced in Il1a2/2 oviduct lysates. During infection, Il1a2/2 oviducts and uterine horns exhibited reduced neutrophil infiltration, and this reduction persisted after the infection resolved. The absence of IL-1a did not compromise CD4 T cell recruitment or function during primary or secondary chlamydial infection. IL-1a is expressed predominantly by luminal cells of the genital tract in response to infection, and low levels of expression persisted after the infection cleared. Ab-mediated depletion of IL-1a in WT mice prevented infection-induced oviduct damage, further supporting a key role for IL-1a in oviduct pathology. [ABSTRACT FROM AUTHOR]