1990 Sir Henry Wellcome medal and prize winner. Leukoregulin: a new biotherapeutic cytokine in the search for more effective anti-viral pharmacologic agents.
This investigation examines whether cytokines, as exemplified by leukoregulin, with their immense potential for biorecognition and target cell modulation as a result of their complex three-dimensional structure, have the potential to provide new directions for biotherapy of infectious disease. Leukoregulin is a naturally occurring immunologic cytokine, secreted by stimulated lymphocytes, which increases membrane permeability and drug uptake in tumor but not in normal cells. This study demonstrates that leukoregulin also increases the plasma membrane permeability of cells acutely infected with herpes simplex type 1 virus and that the increase in membrane permeability is accompanied by a 10- to 100-fold increase in the ability of acyclovir to inhibit the release of infectious virus when the cells are treated with leukoregulin 3 hours after infection with the virus. This is the first demonstration that a cytokine, alone or in combination with anti-viral chemotherapy, can effectively inhibit virus replication in human cells following acute virus infection, which indicates that combination immunotherapy and chemotherapy have the potential to completely inhibit the production of infectious virus by acutely infected human cells.
Evans
C H
CH
National Cancer Institute, Bethesda, MD 20892.
Hooks
J J
JJ
Detrick
B
B
D000212:Acyclovir / Q000627:therapeutic use; D000293:Adolescent; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002463:Cell Membrane Permeability / Q000187:drug effects; D016207:Cytokines / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008222:Lymphokines / Q000494:pharmacology / Q000627:therapeutic use*; D018139:Simplexvirus / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000382:microbiology; D014777:Virus Diseases / Q000188:drug therapy* / Q000382:microbiology; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D016207:Cytokines; D008222:Lymphokines; C044162:leukoregulin; D000212:Acyclovir