Placental immunomodulator ferritin, a novel immunoregulator, suppresses experimental arthritis.
OBJECTIVE
To determine the effect of treatment with C48, the recombinant cytokine-like domain of the novel human placental immunomodulator ferritin (PLIF) immunoregulator, on zymosan-induced arthritis (ZIA) in mice and on adjuvant-induced arthritis (AIA) in rats.


METHODS
The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes. Arthritis was induced by intraarticular injection of zymosan into naive mice and by subcutaneous injection of Mycobacterium tuberculosis into rats. C48 was injected intraperitoneally daily from day 3 to day 9 or from day 7 to day 13 after induction of synovitis by zymosan, and every other day from day 2 to day 14 after induction of AIA. Swelling of the joints and histologic features of the synovium were assessed. Th1 and Th2 cytokines were quantified by enzyme-linked immunosorbent assay.


RESULTS
Both PLIF and C48 significantly inhibited the in vitro immunoreactivity of mouse splenocytes in MLCs. Treatment of ZIA mice and AIA rats with C48 effectively reduced joint swelling. C48 treatment reduced synovial lining thickening, numbers of mononuclear cells and histiocytes, as well as cartilage destruction and bone erosions. In vitro, activated splenocytes from C48-treated ZIA and AIA animals produced significantly higher levels of interleukin-10 (IL-10). In animals with ZIA, this was accompanied by lower levels of tumor necrosis factor and IL-2.


CONCLUSIONS
Human PLIF and C48 were shown to exert cross-species immunosuppressive activity in vitro. The in vivo suppression of articular inflammation in the experimental models of ZIA and AIA was the result of treatment with the antiinflammatory human C48. These results suggest that treatment with C48 may offer an effective immunotherapeutic means of controlling inflammatory polyarthritis.
Weinberger
Abraham
A
Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Halpern
Marisa
M
Zahalka
Muayad A
MA
Quintana
Francisco
F
Traub
Leonid
L
Moroz
Chaya
C
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D047908:Intracellular Signaling Peptides and Proteins; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D010088:Oxidoreductases; D011257:Pregnancy Proteins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D015054:Zymosan
D000276:Adjuvants, Immunologic; C405929:CDK5RAP2 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011257:Pregnancy Proteins; D005293:Ferritins; D015054:Zymosan; C454461:FTH1 protein, human; D010088:Oxidoreductases