KGF pretreatment decreases B7 and granzyme B expression and hastens repairin lungs of mice after allogeneic BMT

We investigated keratinocyte growth factor (KGF) as a pretreatment therapy for idiopathic pneumonia syndrome (IPS) generated as a result of lung damag e and allogeneic T cell-dependent inflammatory events occurring in the earl y peri-bone marrow (BM) transplant (BMT) period. B10.BR (H2(k)) recipient m ice were transplanted with C57BL/6 (H2(b)) BM with spleen cells after letha l irradiation with and without cyclophosphamide conditioning with and witho ut subcutaneous KGF pretreatment. KGF-pretreated mice had fewer injured alv eolar type II (ATII) cells at the time of BMT and exhibited ATII cell hyper plasia at day 3 post-BMT. The composition of infiltrating cells on day 7 po st-BMT was not altered by KGF pretreatment, but the frequencies of cells ex pressing the T-cell costimulatory molecules B7.1 and B7.2 and mRNA for the cytolysin granzyme B (usually increased in IFS) were decreased by KGF. Sera from KGF-treated mice had increases in the Th2 cytokines interleukin (IL)- 4, IL-6, and IL-13 4 days after cessation of KGF administration (i.e., at t he time of BMT). These data suggest that KGF hinders IFS by two modes: 1) s timulation of alveolar epithelialization and 2) attenuation of immune-media ted injury as a consequence of failure to upregulate cytolytic molecules an d B7 ligand expression and the induction of anti-inflammatory Th2 cytokines in situ.