Evaluation of in vivo cytokine expression in EAU-susceptible and resistantrats: a role for IL-10 in resistance?

Messenger RNAs for six cytokines (IL-12p40, IFN-gamma, IL-10, IL-4, TNF-alp ha and TGF-beta 1) expressed in vivo during development of experimental aut oimmune uveitis (EAU) were quantitated by PCR in (uncultured) peripheral ly mphoid cells and in the eyes of EAU-susceptible Lewis and EAU resistant F34 4 rats. Disease was induced by immunization with the R16 peptide of IRBP (i n RT1B(1) haplotype rats) or with whole IRBP (in all haplotypes). In the pe riphery, both Lewis and F344 expressed similar cytokine patterns. In ocular tissues, however, only Lewis expressed elevated type 1 and inflammatory cy tokines (IL-12p40, IFN-gamma and TNF-alpha), coincident with onset and peak of disease. Interestingly, naive F344 rats expressed higher basal levels o f IL-10 mRNA in the eyes, To examine the possible involvement of this pheno menon in resistance, basal levels of IL-10 vs susceptibility to IRBP were c ompared in Lewis, BN, DA, F344 and ACI strains. Lewis, BN and DA were susce ptible and had low levels of IL-10 mRNA in eyes. F344 and ACI were resistan t and expressed high basal levels of IL-10 mRNA. In an in vitro study, reco mbinant rat IL-10 (but not human or mouse IL-10) suppressed lymphocyte prol iferation and IFN-gamma production by primed lymph node cells of R16 immuni zed rats, but did not suppress uveitogenic long-term T-cell lines polarized to the Th1 phenotype, suggesting that mature effector lymphocytes in the r at may lose their ability to be suppressed by IL-10, We propose that higher expression of the IL-10 gene in ocular tissues in some rat strains may rep resent a mechanism that contributes to a higher threshold of resistance to EAU, but this threshold may be overcome by a more mature Th1 effector with a reduced sensitivity to IL-10.