Effect of iCRT14 on lung injury and inflammation of mice challenged with a sublethal dose of influenza virus A/PR/8/34.

<p>C57BL/6J mice were infected with A/PR/8/34 (100 pfu/mouse). Mice euthanized on day 0 of the study were used as a control. Mice received either iCRT14 (50 mg/kg) or vehicle control daily beginning one day prior to infection until day 2 or day 5 after infection. (A) Virus titers in total lung homogenate (n = 6). (B) Average clinical scores; 0 = normal, 1 = ruffled fur, 2 = inactive, 3 = hunched back (n = 10–20). (C) Lung water content as measured by wet-to-dry ratio (n = 4). (D) Total protein in BAL fluid (n = 4). (E) LDH activity in BAL fluid (n = 4). (F) Inflammatory cells in BAL (n = 3–4). The data are presented as the mean ± SE. *<i>p</i> < 0.05 vs. vehicle control on the corresponding days, **<i>p</i> < 0.01 vs. vehicle control on the corresponding days. For (A) and (C), Two-way ANOVA, post hoc sidak was used and 0 time group was not included in analysis due to lack of equal groups. For (B), Student’s t-test was used duo to unequal animal numbers in different groups. (G) Representative H&E photomicrographs from 6 mice are shown. A, B = day 2 vehicle control mice; C, D = day 2 iCRT14 mice; E, F = day 5 vehicle control mice; G, H = day 5 iCRT14 mice. The dark arrowheads in Panels A, C, E, G represent alveolar histiocytic and neutrophil infiltrations with associated hemorrhage. The arrowheads in Panels B, D, F, H represent major airway degeneration/necrosis, histiocytic and neutrophil infiltration. Scale bar = 50 μm.