Background: Elderly women with asthma tend to have a higher risk of severe asthma, which might be at least partly associated with lack of female hormones including progesterone. The progesterone-induced blocking factor (PIBF) is produced from various tissues when exposed to progesterone and plays an important role as an immunomodulatory factor by regulating the activity of NK cells and cytokine production of T cells.

Purpose: We sought to assess the role and therapeutic potential of PIBF in elderly female asthma.

Methods: The expression levels of PIBF and isoforms were measured by multiple reaction monitoring technique in plasma from asthmatics and healthy controls. The ovariectomized C57BL/6N mice were sensitized and challenged with ovalbumin, then the 35 kDa PIBF was intraperitoneally injected before each challenge. We then performed mRNA-sequencing to examine the altered gene expression from the peripheral blood mononuclear cells (PBMCs) induced by treatment with 35 kDa PIBF for 6 and 24 hours, respectively.

Results: PIBF and isoforms were significantly reduced in asthmatics compared to control subjects, and were the lowest in the postmenopausal asthmatics. The 35 kDa PIBF attenuated OVA-induced lung histopathologic changes and the number of inflammatory cells in ovariectomized mice. We found that 273 genes were changed in PBMCs by 35 kDa PIBF treatment (FC=1.5, p<0.05). These were closely related to the immune response, inflammation response, signal transduction.

Conclusion: We suggest PIBF as a novel biomarker and potential therapeutic target for asthma, especially in elderly women.