Rheumatoid arthritis is characterized by chronic
inflammation of the synovial tissue. We examined the effect of
interleukin (IL)-6 neutralization on the expression of
cytochrome P450 or
metallothionein-1/2 (
metallothionein) during chronic phase inflammatory disease using
rheumatoid arthritis model mice, human
T-cell leukemia virus type I (HTLV-I) transgenic mice. Serum
IL-6 concentrations of
arthritis-developed HTLV-I transgenic mice were 129.9+/-26.1 pg/ml. Moreover, signal transducer and activator of transcription (STAT) 1/3 phosphorylations was observed in arthritic HTLV-I transgenic mouse livers. CYP3A11
mRNA was more strongly reduced by the development of
arthritis in HTLV-I transgenic mouse livers as compared with
CYP2C29 or
CYP2E1 mRNAs.
CYP3A protein and
testosterone 6beta-hydroxylation activity also changed in a similar manner to the corresponding CYP3A11
mRNA level. On the other hand,
metallothionein mRNA was significantly induced as compared with that of wild-type or non-arthritic mice.
CYP3A suppression and
metallothionein mRNA overexpression activity seen in the developed arthritic mice returned to the gene conditions of the non-arthritic HTLV-I transgenic mice by
IL-6 antibody at 48 h
after treatment. The present study has revealed that CYP3A11 and
metallothionein expressions are affected by the release of
IL-6 by
arthritis and its systemic circulation, and neutralization of
IL-6 recovered from the down-regulation of CYP3A11
mRNA and the induction of
metallothionein mRNA in arthritic HTLV-I transgenic mice.