Anti-very late antigen-1 monoclonal antibody modulates the development of secondary lesion and T-cell response in experimental arthritis.
Rats injected in the hind paw with a mixture of Mycobacterium butirricum emulsified in mineral oil (FA) developed a severe polyarthritis that shared some immunological features with human rheumatoid arthritis. After this local administration, rats developed a secondary lesion (edema) in the contralateral paw, which is a hallmark of immune system activation. In vivo intravenous treatment with a monoclonal anti-very late antigen (VLA)-1 antibody (HA31/8) significantly reduced the edema formation in the contralateral paw. T cells isolated from contralateral paw draining lymph nodes of FA rats treated with HA31/8 showed a reduced cell proliferation in vitro, after stimulation with concanavalin A. Furthermore FACS analysis showed that the reduction in proliferation was concomitant to a reduction in the number of T cells positive to surface IL-2 receptor expression. Our data indicate that after in vivo treatment with a monoclonal anti-very late antigen-1 antibody, there is a beneficial effect on the development of the secondary lesion, which correlates to the reduced ability of T cells to proliferate in vitro as well as to a reduced surface expression of IL-2 receptor. The association of this antibody to other drugs interfering at other levels in rheumatoid arthritis may open a new therapeutic window.
Ianaro
A
A
Dipartimento di Farmacologia Sperimentale, Napoli, Italy.
Cicala
C
C
Calignano
A
A
Koteliansky
V
V
Gotwals
P
P
Bucci
M
M
Gerli
R
R
Santucci
L
L
Fiorucci
S
S
Cirino
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001170:Arthritis, Infectious / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000276:immunology*; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D009161:Mycobacterium / Q000472:pathogenicity; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D039222:Integrin alpha1beta1; D016023:Integrins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha