title: Inhibition of immune reactions in vivo by liposome associated transforming growth factor (TGF) type beta 1.
abstract: In view of its potent inhibitory capacity on immune cells in culture, we wished to determine the ability of transforming growth factor (TGF) beta 1 to down-regulate immune responses in vivo. Preliminary experiments suggested that, at the doses used, systemic injection of soluble TGF beta 1 could not affect bacterial-induced spleen enlargement in mice. Therefore, we sought to utilize a physiochemical property of this molecule, namely its high pI, to determine possible association between the ligand and preformed liposomes possessing an opposite charge. TGF beta 1 was preferentially associated with negatively charged, but not with neutral, liposomes. These TGF beta 1 associated liposomes were able to deliver a suppressive signal to indicator cells in vitro. Intravenous injection of TGF beta 1, associated with liposomes possessing an opposite charge, into mice immunized with heat-killed Corynebacterium parvum significantly reduced the size of the spleen as well as the number of splenocytes. Systemically administered TGF beta 1 associated liposomes could also inhibit delayed type hypersensitivity reactions to Listeria monocytogenes. These data suggest that appropriately administered, TGF beta 1 can inhibit immune responses in vivo.
authors.affiliation: Maryland Research Laboratories, Otsuka America Pharmaceutical Co., Inc. Rockville 20850.
authors.forename: G
authors.initials: G
authors.lastname: Strassmann
authors.forename: D R
authors.initials: DR
authors.lastname: Bertolini
authors.forename: O
authors.initials: O
authors.lastname: Eidelman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control; D006968:Hypersensitivity, Delayed / Q000517:prevention & control*; D007165:Immunosuppression Therapy / Q000379:methods*; D007275:Injections, Intravenous; D008081:Liposomes; D008088:Listeriosis / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011425:Propionibacterium acnes; D013154:Spleen / Q000033:anatomy & histology; D013163:Splenomegaly / Q000382:microbiology / Q000628:therapy; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D008081:Liposomes; D016212:Transforming Growth Factor beta