Figure 4

Inhibition of IL-1 systemic effects in vivo by intra-colonic administration of IL-1Ra-producing B. subtilis. Upper left: Increase in body temperature in rabbits treated with human recombinant IL-1β (75 ng/kg i.v.) 1 h after a intra-colonic instillation of 2 × 10⁹ live cells of B. subtilis pSM539 (producing IL-1Ra; ●) or pSM214 (β-lactamase control; ○). Data are the mean ± SEM of values from 3 rabbits/group. Difference was statistically significant with p < 0.02 at 40 and 60 min. Upper right: Granulocytosis induced by human recombinant IL-1β in rats. Animals were administered intra-colonically with 1 ml/kg saline () or with the same volume of saline containing 1 × 10⁹ live cells/kg of pSM214 (□) or pSM539 (■). After 2 h animals received 100 ng/kg human recombinant IL-1β i.p. A control group received saline i.p. () instead of IL-1β. All animals were bled 2 h later, and the number of circulating PMN was evaluated cytofluorimetrically. PMN numbers are expressed as percent blood leukocytes and reported as the mean ± SEM of values in 3 rats/group. Lower left: Hypoferremia induced by human recombinant IL-1β in rabbits. Animals received two intra-colonic instillations of 1 ml/kg saline alone () or containing 2 × 10⁹ live cells of B. subtilis pSM539 (producing IL-1Ra; ■) or pSM214 (β-lactamase control; □), 3 h before and 10 min after administration of IL-1β (100 ng/kg i.p.). Control rabbits administered intra-colonically with saline received an i.p. inoculum of saline instead of IL-1β (). Serum iron levels were measured 8 h later. Data are the mean ± SEM of values of 3–25 rabbits, tested in five separate experiments and representative of results obtained at different times after IL-1β inoculum (4–24 h). Lower right: Hypoglycemia induced by human recombinant IL-1β in rats. Animals were administered intra-colonically with 1 ml/kg saline () or with the same volume of saline containing 1 × 10⁹ live cells/kg of pSM214 (□) or pSM539 (■). After 2 h animals received 100 ng/kg human recombinant IL-1β i.p. A control group received saline i.p. () instead of IL-1β. All animals were bled 2 h later, and serum samples were assayed for glucose concentration. Data are reported as the mean ± SEM of values in 3 rats/group.