DISSOCIATION BETWEEN CYTOKINE MESSENGER-RNA EXPRESSION AND PROTEIN-PRODUCTION IN SHIGELLOSIS

In our study, infection with Shigella dysenteriae type 1 (n = 16) or S higella flexneri in adults (n = 5) was associated with a gradual accum ulation of mRNA for interleukin (IL)-1 beta, tumor necrosis factor (TN F)-alpha, IL-6, transforming growth factor-beta, IL-10, IL-4, TNF-beta , interferon (IFN)-gamma and perforin in the rectal biopsy samples dur ing the convalescent stage of the disease demonstrated by in situ hybr idization. In contrast, immunohistochemical staining in rectal tissues of cytokine protein-producing cells at the single-cell level exhibite d a steady-state expression during 2-36 days after the onset of the di sease. The frequency of cytokine mRNA-expressing cells varied in the r ange of 3-100-fold higher than that of the corresponding protein-synth esizing cells. The accumulation of cytokine mRNA. in vivo during shige llosis represented a long-lasting phenomenon throughout the disease co urse, and may be linked to its immunopathogenesis. The results also in dicate that assessment of both protein and mRNA in vivo may provide co mplementary information. Stimulation in vitro of peripheral blood mono nuclear cells from normal healthy donors with Shigella-derived lipopol ysaccharide or shiga toxin was carried out to elucidate the role of Sh igella antigens in the regulation of translation of cytokine-specific mRNA. The incidence of cytokine (IFN-gamma, IL-6 and TNF-alpha) mRNA- and cytokine protein-expressing cells was very similar and congruent a fter both these Shigella-derived stimuli. We could, thus, not find evi dence for shiga toxin-induced down-regulation of cytokine mRNA transla tion as the explanation for the observed discrepancy between cytokine mRNA and protein levels in the tissue biopsies.