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the inflammatory response can be measured in the pouch fluid (Watanabe, 1992).
Of the measures of inflammation studied, only the MMP activity was diminished
by hydroxychloroquine. The absence of an effect on acute leukocyte exudation and
PGE levels are not unexpected as hydroxychloroquine in general has no acute anti-
2
inflammatory effect.
At first, hydroxychloroquine would seem to an agent unlikely to be of much ther-
apeutic use in chronic CPPD disease. However, we know that hydroxychloroquine
has several actions in vitro that may affect the cellular reaction to CPPD crystals
(Baker et al., 1984). Its effects on neutrophils and monocytes seems most likely to
be the mode of action in our in vivo findings. Hydroxychloroquine and related com-
pounds have been shown to stabilize lysosomal membranes, raise intra-lysosomal
pH thus inactivating certain proteases, and can interfere with chemotaxis, phagocy-
tosis and several synthetic processes.
The source of the MMP measured in this study could be either the neutrophils
in the fluid or the pouch lining cells which are capable of producing significant
amounts of MMP. It is not possible to determine whether either or both of these cell
types are affected. We are planning to study each cell type in vitro to determine the
ability of hydroxychloroquine to affect specific cell function.
Our data suggest that hydroxychloroquine can decrease MMP levels induced by
CPPD crystals. This effect in itself may be important in chronic CPPD disease and
could possibly reduce cartilage damage. Our results may also be an indication that
other inflammatory responses that were not measured in our studies are affected
by hydroxychloroquine. The data presented here suggest that clinical studies using
hydroxychloroquine in patients with chronic CPPD disease and in OA associated
with CPPD may be warranted.
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