Inhibition of immune reactions in vivo by liposome associated transforming growth factor (TGF) type beta 1.
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.
Strassmann
G
G
Maryland Research Laboratories, Otsuka America Pharmaceutical Co., Inc. Rockville 20850.
Bertolini
D R
DR
Eidelman
O
O
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
D008081:Liposomes; D016212:Transforming Growth Factor beta