Comparison of immune response to lipopolysaccharide of rabbit does selected for litter size at weaning or founded for reproductive longevity

To evaluate differences in maternal lines to the immune response of reproductive rabbit does, a total of 64 animals of two different lines: (1) founded for hyper-longevity and litter size criteria (LP) and (2) selected for litter size at weaning (V) were used. Females were subjected to three different reproductive efforts: post-partum (PP) mating at first lactation and 9 kits during the second; post-weaning (PW) mating at first lactation and 9 kits during the second; and PW mating at first lactation and 5 kits during the second. At second weaning (30 days PP), an acute response was induced by intravenous infusion of lipopolysaccharide (LPS). LP females seemed to be lower affected during the hyper-acute phase than V females, showing lower plasma glucose content at 1.5 h post infusion (pi) and rectal temperature at 6 h pi; and showed higher ulterior immune response, with higher levels of C-reactive protein at 48 h pi and haptoglobin in plasma from 24 h pi. Survival test conferred a higher risk of culling for V than for LP females during the first hours after challenge. These results may suggest that, regarding immune response to LPS challenge, foundation by hyper-longevity productive criteria lead to obtain a more robust population of rabbit does, characterized by improved response ability. (C) 2013 Elsevier Ltd. All rights reserved.This study has been supported by the Interministerial Commission for Science and Technology (CICYT) from the Spanish Government. Grants Number: AGL2011-30170-C02-01; AGL2011-30170-C02-02), is gratefully acknowledged.Ferrian, S.; Blas Ferrer, E.; Larsen, T.; Sánchez Serrano, JP.; Friggens, NC.; Corpa, JM.; Baselga Izquierdo, M.... (2013). Comparison of immune response to lipopolysaccharide of rabbit does selected for litter size at weaning or founded for reproductive longevity. Research in Veterinary Science. 94(3):518-525. doi:10.1016/j.rvsc.2013.01.008S51852594

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society