Immunization with alum-collagen II complex suppresses the development of collagen-induced arthritis in rats by deviating the immune response.
Collagen-induced arthritis (CIA) is an experimental rat model sharing a number of features with human rheumatoid arthritis (RA). The model is associated with a proinflammatory (TH1) type of immune response and treatments with cytokines associated with TH2 immune responses are beneficial. Since agents with TH1-inducing properties, such as Freund's incomplete adjuvant (FIA), are necessary for disease induction, it is of interest to investigate whether an adjuvant with TH2-inducing properties affects CIA in a different way than does FIA. The authors studied arthritis development in DA rats after immunization with the TH2 stimulatory adjuvant alum adsorbed to rat collagen type II (CII) or collagen II fragments. Such treatments suppressed disease development both prophylactically and therapeutically. This beneficial effect of alum-CII immunization was associated with an increase in the IgG1 anti-CII antibody response as compared to untreated rats or rats pretreated with alum alone. Treatment with alum without the addition of collagen did not have any clinical effect. In addition, alum-CII treated rats had a significantly higher expression of IL-4 mRNA than untreated rats in the lymph nodes, 7 days after CIA induction. The authors suggest that alum-CII induces a TH2 immune response against rat CII which counteracts the development of CIA.
Mattsson
L
L
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
Lorentzen
J C
JC
Svelander
L
L
Bucht
A
A
Nyman
U
U
Klareskog
L
L
Larsson
P
P
D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D003094:Collagen / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003488:Cyanogen Bromide / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
D000534:Alum Compounds; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D015847:Interleukin-4; D003094:Collagen; D003488:Cyanogen Bromide