Intranasal Administration of poly(I:C) and LPS in BALB/c Mice Induces Airway Hyperresponsiveness and Inflammation via Different Pathways

BACKGROUND: Bacterial and viral infections are known to promote airway hyperresponsiveness (AHR) in asthmatic patients. The mechanism behind this reaction is poorly understood, but pattern recognizing Toll-like receptors (TLRs) have recently been suggested to play a role. MATERIALS AND METHODS: To explore the relation between infection-induced airway inflammation and the development of AHR, poly(I:C) activating TLR3 and LPS triggering TLR4, were chosen to represent viral and bacterial induced interactions, respectively. Female BALB/c or MyD88-deficient C57BL/6 mice were treated intranasally with either poly(I:C), LPS or PBS (vehicle for the control group), once a day, during 4 consecutive days. RESULTS: When methacholine challenge was performed on day 5, BALB/c mice responded with an increase in airway resistance. The maximal resistance was higher in the poly(I:C) and LPS treated groups than among the controls, indicating development of AHR in response to repeated TLR activation. The proportion of lymphocytes in broncheoalveolar lavage fluid (BALF) increased after poly(I:C) treatment whereas LPS enhanced the amount of neutrophils. A similar cellular pattern was seen in lung tissue. Analysis of 21 inflammatory mediators in BALF revealed that the TLR response was receptor-specific. MyD88-deficient C57BL/6 mice responded to poly (I:C) with an influx of lymphocytes, whereas LPS caused no inflammation. CONCLUSION: In vivo activation of TLR3 and TLR4 in BALB/c mice both caused AHR in conjunction with a local inflammatory reaction. The AHR appeared to be identical regardless of which TLR that was activated, whereas the inflammation exhibited a receptor specific profile in terms of both recruited cells and inflammatory mediators. The inflammatory response caused by LPS appeared to be dependent on MyD88 pathway. Altogether the presented data indicate that the development of AHR and the induction of local inflammation might be the result of two parallel events, rather than one leading to another

Internet-based psychodynamic versus cognitive behavioral guided self-help for generalized anxiety disorder: a randomized controlled trial

Background: Guided Internet-based cognitive behavior therapy (ICBT) has been tested in many trials and found to be effective in the treatment of anxiety and mood disorders. Generalized anxiety disorder (GAD) has also been treated with ICBT, but there are no controlled trials on guided Internet-based psychodynamic treatment (IPDT). Since there is preliminary support for psychodynamic treatment for GAD, we decided to test if a psychodynamically informed self-help treatment could be delivered via the Internet. The aim of the study was to investigate the efficacy of IPDT for GAD and to compare against ICBT and a waiting list control group. Method: A randomized controlled superiority trial with individuals diagnosed with GAD comparing guided ICBT (n = 27) and IPDT (n = 27) against a no treatment waiting list control group (n = 27). The primary outcome measure was the Penn State Worry Questionnaire. Results: While there were no significant between-group differences immediately after treatment on the main outcome measure, both IPDT and ICBT resulted in improvements with moderate to large within-group effect sizes at 3 and 18 months follow-up on the primary measure in the completer analyses. The differences against the control group, although smaller, were still significant for both PDT and CBT when conforming to the criteria of clinically significant improvement. The active treatments did not differ significantly. There was a significant group by time interaction regarding GAD symptoms, but not immediately after treatment. Conclusions: IPDT and ICBT both led to modest symptom reduction in GAD, and more research is needed. Copyright © 2012 S. Karger AG, Basel

Supplementary Material for: Internet-Based Psychodynamic versus Cognitive Behavioral Guided Self-Help for Generalized Anxiety Disorder: A Randomized Controlled Trial

<b><i>Background:</i></b> Guided Internet-based cognitive behavior therapy (ICBT) has been tested in many trials and found to be effective in the treatment of anxiety and mood disorders. Generalized anxiety disorder (GAD) has also been treated with ICBT, but there are no controlled trials on guided Internet-based psychodynamic treatment (IPDT). Since there is preliminary support for psychodynamic treatment for GAD, we decided to test if a psychodynamically informed self-help treatment could be delivered via the Internet. The aim of the study was to investigate the efficacy of IPDT for GAD and to compare against ICBT and a waiting list control group. <b><i>Method:</i></b> A randomized controlled superiority trial with individuals diagnosed with GAD comparing guided ICBT (n = 27) and IPDT (n = 27) against a no treatment waiting list control group (n = 27). The primary outcome measure was the Penn State Worry Questionnaire. <b><i>Results:</i></b> While there were no significant between-group differences immediately after treatment on the main outcome measure, both IPDT and ICBT resulted in improvements with moderate to large within-group effect sizes at 3 and 18 months follow-up on the primary measure in the completer analyses. The differences against the control group, although smaller, were still significant for both PDT and CBT when conforming to the criteria of clinically significant improvement. The active treatments did not differ significantly. There was a significant group by time interaction regarding GAD symptoms, but not immediately after treatment. <b><i>Conclusions:</i></b> IPDT and ICBT both led to modest symptom reduction in GAD, and more research is needed