An imbalance in mucosal cytokine profile causes transient intestinal inflammation following an animal's first exposure to faecal bacteria and antigens

Intestinal microflora play a critical role in the initiation and perpetuation of chronic inflammatory bowel diseases. In genetically susceptible hosts, bacterial colonization results in rapid‐onset chronic intestinal inflammation. Nevertheless, the intestinal and systemic immune response to faecal bacteria and antigen exposure into a sterile intestinal lumen of a post‐weaned animal with a mature immune system are not understood clearly. This study examined the effects of faecal bacteria and antigen exposure on the intestinal mucosal and systemic immune system in healthy axenic mice. Axenic wild‐type mice were inoculated orally with a crude faecal slurry solution derived from conventionally raised mice and were analysed prior to and then at days 3, 7, 14 and 28 post‐treatment. Ingestion of faecal slurry resulted in a transient, early onset of proinflammatory interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and interleukin (IL)‐17 response that was maximal at day 3. In contrast, the transient release of the anti‐inflammatory cytokines IL‐10 and IL‐4 occurred later and was maximal at day 7. Both responses subsided by day 14. This early cytokine imbalance was associated with a brief rise in colonic and caecal histopathological injury score at day 7. The bacterial antigen‐specific systemic response was found to follow the intestinal immune response with a maximal release of both pro‐ and anti‐inflammatory cytokines at day 7. Thus, first exposure of healthy axenic wild‐type mice to normal faecal flora and antigens results in an early proinflammatory cytokine response and transient colonic inflammation that then resolves in conjunction with a subsequent anti‐inflammatory cytokine profile.     

A study investigating the association of dermatological and infusion reactions to infliximab and infliximab trough levels

BACKGROUND:Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists.OBJECTIVES:To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab.METHODS:Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients’ records were reviewed for dermatological and infusion reactions to infliximab.RESULTS:One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg/mL [interquartile range (IQR) 2.0 μg/mL to 13.3 μg/mL] versus 6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg/mL [IQR 0.1 μg/mL to 5.7 μg/mL]) was lower than that of patients who experienced no such AEs (6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg/mL [IQR 8.8 μg/mL to 17.4 μg/mL]; P<0.001).CONCLUSION:One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events.     

Does the level of reproductive knowledge specific to inflammatory bowel disease predict childlessness among women with inflammatory bowel disease?

BACKGROUND:

Women with inflammatory bowel disease (IBD) may choose to remain childless due to a lack of IBD-specific reproductive knowledge.

OBJECTIVES:

To examine the effects of IBD-specific reproductive knowledge and discussion of family planning with a physician on childlessness among women with IBD.

METHODS:

Female IBD patients 18 to 45 years of age completed the Crohn’s and Colitis Pregnancy Knowledge questionnaire (CCPKnow), and answered questions regarding reproductive history, plans to have children and discussion of family planning with a physician. CCPKnow scores were grouped according to poor (0 to 7), adequate (8 to 10), good (11 to 13) and very good (14 to 17).

RESULTS:

Of 434 eligible women, 248 (57.1%) completed the questionnaires. Of these 248 women, 51.6% were childless and, among these, 12.9% were voluntarily childless and 12.1% were trying to become pregnant. Childless women had a lower median CCPKnow score than women with children (6.0 versus 8.0; P=0.001). After adjusting for current age and marital status, each one point increase in the CCPKnow score corresponded to 8% lower odds of childlessness (OR 0.92 [95% CI 0.86 to 0.99]), 9% lower odds of voluntary child-lessness (OR 0.91 [95% CI 0.79 to 1.0]) and 20% higher odds of trying to become pregnant (OR 1.2 [95% CI 1.0 to 1.4]). Discussion of family planning with a gastroenterologist corresponded to 72% lower odds of a poor CCPKnow score (OR 0.28 [95% CI 0.15 to 0.53]) and of voluntary childlessness (OR 0.28 [95% CI 0.057 to 1.3]).

CONCLUSION:

In the present study, higher IBD-specific reproductive knowledge lowered the odds of childlessness among women with IBD. Discussion of family planning with a physician was associated with higher CCPKnow scores and lower odds of voluntary childlessness.     

Parent–Adolescent Cross-Informant Agreement in Clinically Referred Samples: Findings From Seven Societies

To conduct international comparisons of parent–adolescent cross-informant agreement in clinical samples, we analyzed ratings on the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) for 6,762 clinically referred adolescents ages 11–18 from 7 societies (M = 14.5 years, SD = 2.0 years; 51% boys). Using CBCL and YSR data, we asked the following questions: (a) Do parents report more problems for their adolescent children than the adolescents report about themselves? (b) How do cross-informant correlations (rs) for scale scores differ by problem type and by society? (c) How well do parents and adolescents, on average, agree regarding which problems they rate as low, medium, or high? (d) How does within-dyad item agreement vary within and between societies? (e) How do societies vary in dichotomous cross-informant agreement with respect to the deviance status of the adolescents? CBCL and YSR scores were quite similar, with small and inconsistent informant effects across societies. Cross-informant rs averaged .47 across scales and societies. On average, parents and adolescents agreed well regarding which problem items received low, medium, or high ratings (M r = .87). Mean within-dyad item agreement was moderate across all societies, but dyadic agreement varied widely within every society. In most societies, adolescent noncorroboration of parent-reported deviance was more common than parental noncorroboration of adolescent-reported deviance. Overall, somewhat better parent–adolescent agreement and more consistency in agreement patterns across diverse societies were found in these seven clinical samples than in population samples studied using the same methods.