title: Cell-mediated immunity is enhanced by cytostatic drugs continuously released at the site of antigenic stimulation.
abstract: Immunopotentiation by cytostatic drugs continuously released from osmotic minipumps, was investigated in a guinea-pig contact-sensitivity model. These pumps are designed to release their content within a period of 7 days. Vepeside (VP-16) and 5-fluorouracil were released into oxazolone-stimulated lymph nodes by subcutaneous implantation of pumps containing either of these drugs. The pumps were implanted at the intended sensitization site, 2 days before sensitization. Strong potentiation of T-cell-mediated immunity, evaluated by delayed-type hypersensitivity measurements, was observed with both drugs tested. Daily injections with VP-16 also caused an enhancement of the immune response. However, daily injections with 5-fluorouracil, a drug assumed to be cell-cycle-specific in its action, failed to potentiate delayed hypersensitivity to oxazolone. Intralesional administration of cytostatic drugs has been put forward as an effective treatment modality in various types of cancer. Therapeutic effects may depend on both local tumor cytotoxic and immunopotentiating activities. Our present results suggest that osmotic minipumps can be applied to broaden the applicability and effectiveness of local chemotherapy.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, the Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Claessen
authors.forename: H
authors.initials: H
authors.lastname: Valster
authors.forename: H
authors.initials: H
authors.lastname: Bril
authors.forename: S
authors.initials: S
authors.lastname: Meyer
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003877:Dermatitis, Contact / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006168:Guinea Pigs; D007111:Immunity, Cellular / Q000187:drug effects*; D007260:Infusion Pumps; D010080:Oxazoles / Q000276:immunology*; D010081:Oxazolone / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D010080:Oxazoles; D010081:Oxazolone; D005047:Etoposide; D003520:Cyclophosphamide; D005472:Fluorouracil