The objective of the present investigation was to examine the effects of an irreversible inhibitor of
ornithine decarboxylase (2R,5R)-6-heptyne-2,5,diamine (
methylacetylenic putrescine, MAP) on experimentally induced
arthritis in mice. MAP (0.5-0.05%) was administered in
drinking water to DBA/1 mice immunized with native chick
type II collagen (CII). The development of
arthritis was inhibited only in those mice receiving 0.5% MAP; lower doses were ineffective.
Putrescine and
spermidine levels were decreased and
spermine levels were increased in spleen and lymph node cells from
drug-treated mice compared to control arthritic mice. Furthermore, when control mice were developing
arthritis, serum anti-CII antibody levels were lower in the MAP-treated group. MAP inhibited antibody production early in the immune response to CII; there was an association between inhibition of antibody production and inhibition of the development of
arthritis. When MAP was discontinued, the nonarthritic,
drug-treated mice did not develop the disease. Late administration of MAP (beginning 19 days after CII immunization) did not affect the incidence or the severity of the
arthritis.
Cyclophosphamide treatment begun at the same time significantly inhibited the development of the disease. In vitro T cell responses to denatured
type II collagen (dCII) in untreated and MAP-treated mice were examined 14 days after immunization with CII. This is a time of peak T cell responsiveness in untreated animals. MAP treatment had no effect on the T cell response to dCII. These results indicate that MAP can prevent the development of CII-induced
arthritis, possibly by inhibiting the
autoantibody response. Therefore, inhibitors of
polyamine biosynthesis deserve further investigation as potential
immunosuppressive agents.