Intratumoral injection of lipopolysaccharide causes regression of subcutaneously implanted mouse glioblastoma multiforme

OBJECTIVE: Anecdotal reports documented extended survival times for patient s who developed infections at the site of resection of malignant gliomas. H ypothesized mechanisms for this phenomenon include immune responses trigger ed by lipopolysaccharide (LPS). This investigation assessed whether LPS cou ld produce tumor regression in an in vivo model of malignant glioma. METHODS: Delayed brain tumor cells (2 x 10(6)) were injected subcutaneously into female BALB/c mice. LPS (300-500 mug) was injected intratumorally or subcutaneously at a contralateral site on Days 10, 17, and 24. Control anim als received phosphate-buffered saline intratumorally or subcutaneously. Mi ce were killed on Day 28, and tumors were removed. Mean tumor masses for co ntrol animals and the two LPS-treated groups (intratumoral or contralateral subcutaneous treatment) were compared. Histological assessments of treated and control tumors were performed. RESULTS: Complete or nearly total tumor regression was achieved in all 20 m ice with subcutaneous delayed brain tumor cell tumors treated intratumorall y with 400 mug of LPS (mean tumor mass of 0.09 +/- 0.38 g versus 2.42 +/- 2 .46 g for control animals, P < 0.0001). Intratumoral administration of 300 <mu>g of LPS or subcutaneous injection of 300 or 400 mug of LPS at a contra lateral site resulted in less consistent regression of subcutaneous tumors. Administration of 500 Ecg of LPS resulted in tumor regression similar to t hat observed with lower doses but was limited by treatment-related deaths i n 40% of animals. Histological assessment revealed lymphocytic infiltration of LPS-treated tumors. CONCLUSION: Intratumoral injections of LPS caused dramatic regression of su bcutaneously implanted delayed brain tumor cell mouse gliomas. Investigatio n of this antitumoral effect may improve treatment responses for patients w ith malignant gliomas.