Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis.
In the enclosed study we have examined the expression and contribution of specific chemokines, macrophage inflammatory protein 1 alpha (MIP-1 alpha) and macrophage inflammatory protein 2 (MIP-2), and interleukin 10 (IL-10) during the evolution of type II collagen-induced arthritis (CIA). Detectable levels of chemotactic cytokine protein for MIP-1 alpha and MIP-2 were first observed between days 32 and 36, after initial type II collagen challenge, while increases in IL-10 were found between days 36 and 44. CIA mice passively immunized with antibodies directed against either MIP-1 alpha or MIP-2 demonstrated a delay in the onset of arthritis and a reduction of the severity of arthritis. On the contrary, CIA mice receiving neutralizing anti-IL-10 antibodies demonstrated an acceleration of the onset and an increase in the severity of arthritis. Interestingly, anti-IL-10 treatment increased the expression of MIP-1 alpha and MIP-2, as well as increased myeloperoxidase (MPO) activity and leukocyte infiltration in the inflamed joints. These data suggest that MIP-1 alpha and MIP-2 play a crucial role in the initiation and maintenance, while IL-10 appears to play a regulatory role during the development of experimental arthritis.
Kasama
T
T
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Strieter
R M
RM
Lukacs
N W
NW
Lincoln
P M
PM
Burdick
M D
MD
Kunkel
S L
SL
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000378:metabolism; D003094:Collagen / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D007116:Immunization, Passive; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D015846:Monokines / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D016207:Cytokines; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D016753:Interleukin-10; D003094:Collagen