Brain, Behavior, and Immunity最新文献

Psoriasis is a chronic immune-mediated skin disorder characterized by intense local inflammation, epidermal hyperplasia, and leukocyte infiltration. Current treatment approaches for psoriasis aim to alleviate symptoms and prevent disease progression, including systemically administered drugs with whole body side effects. Despite some advances in psoriasis treatment, success has been quite limited. To begin to address this challenge, we undertook an initial investigation of whether transcutaneous delivery of an endogenous anti-inflammatory cytokine could provide an effective, local treatment of psoriatic-like skin conditions. To do this, we utilized a previously documented rodent model of psoriasis, induced via a single topical application of Imiquimod (IMQ) to the shaved back of rats. The therapeutic approach used for this initial investigation was delivery of plasmid DNA encoding rat interleukin-10 (pDNA-rIL10), a non-viral gene therapy approach previously shown to be effective in suppressing neuroinflammatory disorders after localized delivery either intracerebrally or intrathecally. Translation of this CNS therapeutic for use in psoriatic-like skin disorders required reformulation to enable transcutaneous delivery. Toward that end, pDNA-rIL10 was topically applied in Lipoderm HMW, a base explicitly designed to deliver higher molecular weight compounds into skin. Here we show that a single topical application of pDNA-rIL10 in Lipoderm HMW was effective in decreasing mRNA levels of pro-inflammatory cytokines as well as reducing the recruitment of T-cells to IMQ-treated skin. Furthermore, this transcutaneous IL-10 gene therapy decreased signs of skin inflammation, reflected by reduced erythema. Moreover, the results provide an initial indication that IL10 may stimulate hair regrowth in psoriatic-like skin.

Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between tissues and SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed the presence of increased SARS-CoV-2 genomic RNA in diverse tissues of delta-infected GSH compared to the omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection.

Background: Exercise promotes immunometabolic health and is increasingly recognized as an effective depression treatment. Exercise may be beneficial for patients with immunometabolic depression (IMD), who experience inflammatory and metabolic dysregulations and may respond less to antidepressants. This secondary analysis of the MOTAR study compared the effects of running therapy and antidepressants on IMD features among patients with depression and/or anxiety disorder. We additionally assessed whether baseline IMD moderated intervention effects on depression.

Methods: Participants received 16 weeks of group-based running therapy (N = 96) or escitalopram/sertraline (N = 45) in a partially randomized patient preference design. IMD features included atypical, energy-related symptom (AES) severity, inflammation index (CRP, IFN-γ, IL-6, TNF-α), metabolic syndrome index, three metabolite principle components (PC) (derived from 73 metabolites) and a composite IMD index.

Results: Interventions differed in changes in the metabolic syndrome index (d = 0.59, p = 0.026) and IMD index (d = 0.85, p < 0.001). While running therapy decreased both outcomes, the antidepressant group showed an increased IMD index. Although groups did not differ statistically significant in changes in AES severity, inflammation index, and metabolite PC1, results indicated a consistent trend towards greater improvement with running therapy across these outcomes as well (d = 0.38 to 0.52). Baseline IMD did not moderate intervention effects on depression outcomes.

Conclusions: This study suggests that exercise more effectively targets the IMD dimension than antidepressants. Patients with IMD did not benefit more from running therapy than antidepressants in terms of reductions in depression. Exercise should be considered an alternative or complementary treatment to particularly reduce IMD features in depressed patients.

Trial registration: Trialregister.nl Number of identification: NTR3460.