Ingested (oral) tocilizumab inhibits EAE.
BACKGROUND
Blocking the activity of IL-6 can inhibit autoimmune diseases such as rheumatoid arthritis and Crohn's disease.


OBJECTIVE
We examined whether an antibody against IL-6, tocilizumab (TCZ) (Actemra®), used clinically in rheumatoid arthritis (RA) would have similar anti-inflammatory effects in EAE after oral administration.


METHODS
B6 mice were immunized with MOG peptide 35-55 and gavaged with control saline or TCZ during ongoing disease. Splenocytes, CD4(+) T cells or macrophages/monocyte lineage cells (CD11b(+)) from control fed or TCZ fed mice were adoptively transferred into active MOG peptide 35-55 immunized recipient mice during ongoing disease. Actively fed and recipient mice were examined for disease inhibition, inflammation, and cytokine responses.


RESULTS
Ingested (oral) TCZ inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TCZ fed donors protected against actively induced disease and decreased inflammation. There was a decrease in IL-6 in actively treated spleen, decrease in TNF-α, Th1-like cytokine IL-12 and increase in Th2-like cytokine IL-10 in active fed and adoptively treated recipients.


CONCLUSIONS
Ingested (orally administered) TCZ can inhibit disease, CNS inflammation, decrease pro-inflammatory Th1-like cytokines and increase Th2-like anti-inflammatory cytokines.
Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States. Electronic address: staley.a.brod@uth.tmc.edu.
Staley A
SA
Brod
Department of Neurology, University of Texas-Houston, Health Science Center, 6431 Fannin St, Houston, TX 77030, United States.
Victoria L
VL
Bauer
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007114:Immunization; D007249:Inflammation / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha
D061067:Antibodies, Monoclonal, Humanized; D039481:CD11b Antigen; D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C502936:tocilizumab
Adoptive transfer; Antibody; EAE; Oral proteins; Tocilizumab