Therapeutic effect of transforming growth factor-beta 2 on actively induced EAN but not adoptive transfer EAN.
A possible effect of transforming growth factor type-beta 2 (TGF-beta 2) on autoimmune inflammation of the peripheral nervous system (PNS) was evaluated in experimental autoimmune neuritis (EAN) in Lewis rats, a disease model of the human Guillain-Barré syndrome. First, EAN was actively induced by immunization with a neuritogenic peptide corresponding to amino acids 53-78 of the bovine P2 protein. Intraperitoneal (i.p.) administration of 5 micrograms TGF-beta 2 per day after onset of clinical disease shortened the duration and ameliorated the severity of EAN compared to sham-injected control animals. Inflammatory infiltration and demyelination was significantly reduced in sciatic nerves of TGF-beta-treated animals, although expression of major histocompatibility complex (MHC) class II antigens was not down-regulated. Second, EAN was induced by adoptive transfer (AT) of activated P2-specific T-line cells (AT-EAN). Daily injections of 5 micrograms TGF-beta 2 i.p., beginning on the day of first clinical signs, failed to modify the clinical course of AT-EAN, although the antigen-induced activation of the neuritogenic T-line cells used for induction of disease was found to be partially sensitive to the inhibitory effect of TGF-beta in vitro. The experiments indicate that TGF-beta 2 holds promise as a therapeutic agent to combat autoimmunity in the PNS. They also suggest that the therapeutic efficacy of TGF-beta on rapidly developing disease such as AT-EAN is limited, as with other non-specific immunosuppressive drugs.
Jung
S
S
Department of Neurology, Julius-Maximilians-Universität Würzburg, Germany.
Schluesener
H J
HJ
Schmidt
B
B
Fontana
A
A
Toyka
K V
KV
Hartung
H P
HP
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007114:Immunization; D017710:Lymphocyte Transfusion; D008264:Macrophages / Q000473:pathology; D004676:Myelin Basic Protein / Q000276:immunology; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000627:therapeutic use; D012584:Sciatic Nerve / Q000473:pathology; D013127:Spinal Nerves / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta