Linomide suppresses experimental autoimmune neuritis in Lewis rats by inhibiting myelin antigen-reactive T and B cell responses

Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on experimental autoimmune neuritis (EAN), a CD4+ T cell-mediated animal model of acute Guillain–Barré syndrome (GBS) in humans. EAN induced in Lewis rats by inoculation with bovine peripheral nervous system (PNS) myelin and Freund's complete adjuvant was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical EAN, as well as the severity of EAN symptoms. These clinical effects were associated with dose-dependent down-modulation of PNS antigen-induced T and B cell responses and with suppression of the proinflammatory cytokines IL-12, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) mRNA. In PNS sections, Linomide suppressed IL-12 and TNF-α, and up-regulated IL-10 mRNA expression. These findings suggest that Linomide could be useful in certain T cell-dependent autoimmune diseases

Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes

Effect of hydrolyzed infant formula vs conventional formula on risk of type 1 diabetes the TRIGR randomized clinical trial

IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 117 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 117 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 211759 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 117 diabetes recruited from May 2002 to January 2007 in 78 study centers in 1175 countries; 11708117 were randomized to be weaned to the extensively hydrolyzed casein formula and 117078 to a conventional formula. The follow-up of the participants ended on February 28, 201177. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20%of the casein hydrolysate. The minimum duration ofstudy formula exposure was 60 days by6 to 8 months ofage. MAINOUTCOMES ANDMEASURES Primary outcome was type 117 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 211759 newborn infants (11702117 female [47.3%]) who were randomized, 117744 (80.8%) completed the trial. The participants were observed for a median of 117117.5 years (quartile [Q] 117-Q3, 1170.2-1172.8). The absolute risk of type 117 diabetes was 8.4% among those randomized tothe casein hydrolysate (n = 9117) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -117.6% to 3.2%]). The hazard ratio for type 117 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 117.117 (95% CI, 0.8 to 117.5; P =.46). The median age at diagnosis of type 117 diabetes was similar in the 2 groups (6.0 years [Q117-Q3, 3.117-8.9] vs 5.8 years [Q117-Q3, 2.6-9.117]; difference, 0.2 years [95% CI, -0.9 to 117.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 117 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 117 diabetes after median follow-up for 117117.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 117 diabetes