Reply

S. Bas and C. Gabay

Division of Rheumatology, Department of Internal Medicine, University Hospital, Geneva, Switzerland

Correspondence to: S. Bas, Division of Rheumatology, Hôpital Beau-Séjour, 1211 Geneve 14, Switzerland. E-mail: sylvette.bas{at}hcuge.ch

We thank Drs Cuchacovich and Espinoza for their interesting comments.

Commercial ELISA kits, including the Quantikine kit, developed for serum or plasma measurements, have been widely used to determine levels of cytokines in synovial fluid (SF) [1]. In a comparative study, cytokine measurements have been performed in SF, plasma and culture supernatants with commercial ELISA kits from seven companies (one of them being R & D Systems) and similar findings were obtained with the three kinds of samples [2].

The lower levels of SF interleukin (IL)-10 in reactive arthritis (ReA) patients compared with rheumatoid arthritis (RA) patients have also been reported by other groups (spondylarthropathies, mean 4.5 U/ml vs RA, mean 84.6 U/ml [3]; ReA, median 10 pg/ml vs RA, median 30.3 pg/ml [4]; seronegative spondylarthropathies, mean 9.2 pg/ml vs RA, mean 88.4 pg/ml [5]). In two of these studies, where the SF levels of interferon (IFN)-{gamma} were reported the SF IFN-{gamma}/IL-10 ratios were also higher in ReA [4] patients and seronegative spondylarthropathy [5] patients.

These data are in contrast to the relative abundance of synovial IL-10 mRNA reported by Kotake et al. [6] in patients with Chlamydia-associated arthritis. However, our patients with Chlamydia trachomatis ReA had a mean duration of arthritis (1.4 months) shorter than that of the patients in this report (3 months). Thus, the discrepant results could be explained if IL-10 production was delayed in patients with ReA or if there is regulation at the level of translation. These differences could also be explained by differences in drug therapy.

IL-10 gene knockout mice clear Chlamydia infection more rapidly than normal mice. However, lung infection with the mouse pneumonitis biovar of C. trachomatis [7] probably differs from human ReA because there are human serovars of C. trachomatis. For instance, Perry et al. [8] showed that all human serovars of C. trachomatis were much more sensitive to the direct inhibitory actions of IFN-{gamma} than the mouse pneumonitis strain.

The low IL-10 concentrations and high IFN-{gamma}/IL-10 ratios observed in SF from ReA patients could indicate an autoimmune response to self heat shock protein (hsp) 60. Indeed, in mice immunized with both mouse and C. trachomatis hsp60, lymphocytes proliferated strongly in response to mouse hsp60, secreted 6-fold less IL-10 and exhibited a 12-fold increase in the IFN-{gamma}/IL-10 ratio compared with mice immunized with mouse hsp60 alone [9]. These findings suggest than an increased IFN-{gamma}/IL-10 ratio, as observed in ReA patients, may contribute to the Chlamydia-induced immunopathology.

IL-4 and IL-17 are certainly cytokines of interest but we could not determine their levels because sufficient SF was not available.

References

  1. Manicourt DH, Poilvache P, Van Egeren A, Devogelaer JP, Lenz ME, Thonar EJ. Synovial fluid levels of tumor necrosis factor alpha and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis. Arthritis Rheum 2000;43:281–8.[CrossRef][ISI][Medline]
  2. Ledur A, Fitting C, David B, Hamberger C, Cavaillon JM. Variable estimates of cytokine levels produced by commercial ELISA kits: results using international cytokine standards. J Immunol Methods 1995;186:171–9.[CrossRef][ISI][Medline]
  3. Cush JJ, Splawski JB, Thomas R et al. Elevated interleukin-10 levels in patients with rheumatoid arthritis. Arthritis Rheum 1995;38:96–104.[ISI][Medline]
  4. Ribbens C, Andre B, Kaye O, et al. Increased synovial fluid levels of interleukin-12, sCD25 and sTNF-RII/sTNF-RI ratio delineate a cytokine pattern characteristic of immune anthropathies. Eur Cytokine Netw 2000;4:699–76.
  5. Moller B, Nguyen TT, Kessler U, Kaltwasser JP, Hoelzer D, Ottmann OG. Interleukin-10 expression: is there a neglected contribution of CD8+ T cells in rheumatoid arthritis joints? Clin Exp Rheumatol 2002;20:813–22.[Medline]
  6. Kotake S, Schumacher HR Jr, Arayssi TK et al. Gamma interferon and interleukin-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis and undifferentiated oligoarthritis and from healthy volunteers. Infect Immun 1999;67:2682–6.[Abstract/Free Full Text]
  7. Yang X, Gartner J, Zhu L, Wang S, Brunham RC. IL-10 gene knockout mice show enhanced Th1-like protective immunity and absent granuloma formation following Chlamydia trachomatis lung infection. J Immunol 1999;162:1010–7.[Abstract/Free Full Text]
  8. Perry LL, Su H, Feilzer K et al. Differential sensitivity of distinct Chlamydia trachomatis isolates to IFN-gamma-mediated inhibition. J Immunol 1999;162:3541–8.[Abstract/Free Full Text]
  9. Yi Y, Yang X, Brunham RC. Autoimmunity to heat shock protein 60 and antigen-specific production of interleukin-10. Infect Immun 1997;65:1669–74.[Abstract]
Accepted 20 May 2003





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