To the Editor:

We read with interest the report by Busso et al describing their study of the role of protease-activated receptor 2 (PAR-2) in various models of arthritis (1). Their findings provide immunohistochemical evidence of a potential role of PAR-2 in the pathogenesis of rheumatoid arthritis. We have previously observed that monarthritis induced by Freund's complete adjuvant is substantially attenuated in PAR-2–knockout mice (2), but Busso and colleagues were unable to reproduce our findings in this model, which they attribute to differences in the genetic background or in the gene construct of the PAR-2 deletion.

We would ascribe an alternative, more plausible, explanation for this discrepancy, based on our past experience with this model. Busso et al report that they induced arthritis in their study mice by intraarticular injection of Freund's complete adjuvant into one knee, citing our article (2) for the protocol they followed. The protocols are in fact not the same, since our protocol involved both intra- and periarticular injection of Freund's complete adjuvant, and indeed this difference is the most likely reason for their inability to replicate our earlier findings. Importantly, we observed in experiments preliminary to our earlier study (2) that injection of adjuvant by only an intraarticular route yielded a small response in wild-type C57BL/6J mice, compared with the modified protocol described in our report (Figure 1). The absence of chronic arthritis in response to insufficient inflammatory challenge, coupled with the residual inflammatory response we observed in PAR-2–knockout mice (2), would explain the lack of observable difference between wild-type mice and PAR-2–knockout mice reported by Busso et al.

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Figure 1. Arthritic response, assessed by change in joint diameter, in mice treated only with intraarticular injection of Freund's complete adjuvant (FCA 1) versus mice treated with both intraarticular and periarticular injection of this agent (FCA 2). Values are the mean and SEM.

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William Ferrell MD*, Elizabeth Kelso BSc*, John Lockhart PhD†, Lynette Dunning BSc†, * University of Glasgow, Glasgow, UK, † University of Paisley, Paisley, UK.