Progesterone (P4) protects adult female mice against lethal IAV infection.

<p>Adult female mice were ovariectomized, treated with placebo (-P4) or exogenous P4 (+P4), and inoculated with lethal IAV or mock-infected. Serum was collected at 3, 5, 7, and 21 days post-inoculation (dpi) and P4 concentrations (mock n = 5, IAV n = 20–22 [i.e., n = 5–7 per dpi]) were analyzed by radioimmunoassay, and uterine horns (mock n = 13, IAV = 35–38 i.e., n = 12–14 dpi time-point) were weighed (A). Lungs were harvested at days 3, 5, or 7 dpi and mRNA expression of the progesterone receptor (<i>Pr</i>) was measured and normalized to GAPDH and mock-infected animals using the ΔΔCt method (B). Values for each measure (A and B) did not differ between dpi and are shown as aggregates. Mice (-P4 n = 20, +P4 n = 10) were monitored daily for changes in rectal body temperature (C) and survival (D) for 21 dpi. Infectious virus titers in the lungs were measured at 3, 5, or 7 dpi (E; n = 8-10/treatment/dpi). The correlation between changes in body temperature and virus titers at 7dpi, as a measure of disease tolerance, was quantified using a linear regression model (F; n = 12/treatment). H&E stained lung sections collected at 7dpi from mock-infected (G, panel 1 and 2) and IAV-infected females (G, panels 3–6) were scored for inflammation. Alveolitis (G panel 3 and 4, indicated by black triangles) and edema are shown (G panels 5 and 6, indicated by black stars), as well as corresponding histopathogical scores on a scale from 0–3 (H, n = 3/treatment, 10 fields/animal, 10X magnification). Data represent means ± SEM from two independent experiments and significant differences are represented by asterisks (*).