Sphingosine 1-phosphate receptor (S1PR) agonism is effective at therapeutic time points and is pertussis toxin (PT) insensitive. C57BL/6 animals were inoculated with Bordetella pertussis or a sham inoculum of phosphate-buffered saline (PBS) (sham) before treatment with CYM-5442 1 hour after inoculation (CYM [1 h]), CYM-5442 at 72 hours after inoculation (CYM [72 h]), or vehicle at 72 hours after inoculation (vehicle). Lung RNA was isolated 4 days after inoculation for assessment of transcriptional levels of interleukin 1β (IL-1β) (A) or interferon (IFN) γ (B) with quantitative polymerase chain reaction. C, Lung pathology was assessed after hematoxylin-eosin staining, by 2 independent researchers based on the degree and breadth of bronchovascular bundle inflammation and tissue consolidation. D, S1PR agonist-mediated suppression of inflammatory pathology is not PT sensitive. At 48 hours before inoculation, animals received either PT pretreatment (100 ng) or PBS control. All animals were then inoculated with B. pertussis before treatment 1 hour later with S1PR agonist (AAL-R) or vehicle control. Results are presented as mean and SDs. *P < .05; †P < .01; ‡P < .005; §P < .001.