Modulation of systemic cytokine levels by implantation of alginate encapsulated cells.
The availability of cell lines that are transfected with IL-4, IL-5 and IFN-gamma cytokine genes permits the prolonged in vivo delivery of functional cytokines in relatively large doses for the modulation of specific immune responses. Often the transfected cells are xenogeneic or allogeneic to the experimental animal and have to be encapsulated in such a way that no cellular response by the host will be induced. Alginate has proven to be a simple matrix for encapsulating cells under mild conditions suitable for in vivo implantation. Encapsulated cells express the transfected IL-4 gene for at least 14 days after in vivo implantation and were shown to be functional during that period by modulating ongoing IgE responses. The application of adherent growing transfected cells permits dose-response titrations and provides an easy method for local and systemic cytokine delivery. Alternatively, hybridoma cells can be encapsulated and the secreted antibody monitored in the serum. It was found that no host immune response was triggered by alginate encapsulated cells. The efficiency of treatment by encapsulated hybridoma cells was shown to be equivalent to that of injecting purified antibodies.
Savelkoul
H F
HF
Department of Immunology, Erasmus University, Rotterdam, Netherlands.
van Ommen
R
R
Vossen
A C
AC
Breedland
E G
EG
Coffman
R L
RL
van Oudenaren
A
A
D000464:Alginates; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004339:Drug Compounding; D005260:Female; D006825:Hybridomas / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008863:Microspheres; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014162:Transfection
D000464:Alginates; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E