Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study

Object. Commonly used for management of cerebral edema in patients with bra in tumors, steroid medications also have immunosuppressive functions. To ch aracterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model. Methods. Freshly prepared 11-day-old intracranial C6 tumors that had been e xcised from dexamethasone-treated and untreated rats were labeled ex vivo w ith monoclonal antibodies against CD11b/c, CD45, and CD8a antigens. The ext ent of microglia (CD11b/c-highly positive, CD45-slightly positive cell), ma crophage (CD11b/c-highly positive, CD45-highly positive cell), lymphocyte ( CD11b/c-negative, CD45-highly positive cell), and cytotoxic T-cell (CD8a-po sitive cell) infiltration into each rat's tumor, tumor periphery, and contr alateral tumor-free hemisphere was analyzed using flow cytometry. Microglia and lymphocytes constituted a significant component of infiltrati ng cells in this model, comprising 23 +/- 3% and 33 +/- 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 +/- 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose de xamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of mi croglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. inc reasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory e ffect on microglia invasion. Macrophage infiltration of tumors was not inhi bited at the dexamethasone doses used in this study (p = 0.42). Conclusions. Flow cytometry is a valuable technique for characterizing tumo r-associated inflammatory cells in gliomas. Even at low doses, dexamethason e was found to inhibit significantly the infiltration of brain tumors by ly mphocytes and microglia. These findings should be considered when experimen tal immunotherapeutic strategies are evaluated for clinical application.