Neuroimmunomodulation最新文献

Introduction: Rheumatoid arthritis (RA) can be comorbid with psychiatric symptoms. Brain abnormalities in RA patients and in arthritis models have been reported. However, it remains unclear when these abnormalities occur and where they are distributed. In this study, we analyzed spatiotemporal changes in gene expression in the brains of mice with collagen-induced arthritis (CIA).

Methods: Mice were divided into three groups: (i) CIA (all mice developed arthritis on day 35): complete Freund's adjuvant (CFA) and type II collagen at initial immunization, and incomplete Freund's adjuvant (IFA) and type II collagen at booster immunization; (ii) C(+/-) (50% mice developed arthritis on day 35): only IFA at booster immunization; and (iii) C(-/-) (no arthritis): only CFA at initial immunization and only IFA at booster immunization. Whole brains were collected at ten stages of arthritis and divided into six sections. Real-time polymerase chain reaction was performed using RNA extracted from the brain, and the expression of proinflammatory cytokines and glial markers was semi-quantified. Arthritis score, body weight, and food and water intakes were recorded and analyzed for correlations with brain gene expression. We also investigated the effect of interleukin-6 (IL-6) injection in the olfactory bulbs (OBs) on the food intake.

Results: After booster immunization, a transient increase in Integrin subunit α-M and IL-1β was observed in multiple areas in CIA. IL-6 is persistently expressed in the OB before the onset of arthritis, which is correlated with body weight loss and decreased food intake. This change in the OB was observed in the C(+/-) but not in the C(-/-) groups. In the C(+/-) group, non-arthritic mice showed the same changes in the OB as the arthritic mice. This elevation in IL-6 levels persisted throughout the chronic phase until day 84. In addition, IL-6 injection into the OB reduced food intake.

Conclusion: Persistent elevation of IL-6 in the OB from the early stage of arthritis may be an important finding that might explain the neuropsychiatric pathophysiology of RA, including appetite loss, which is present in the early stages of the disease and manifests as a variety of symptoms over time.

Introduction: In an attempt to avoid contact with infectious individuals, humans likely respond to generalized rather than specific markers of disease. Humans may thus perceive a noninfectious individual as socially less attractive if they look (e.g., have facial discolouration), move (e.g., have a slower walking pace), or sound (e.g., sneeze) sick. This pilot study tested whether humans are averse to the body odour of noninfectious individuals with a low-grade systemic inflammation.

Methods: We collected the axillary body odour of individuals with severe seasonal allergy (N = 14) and healthy controls (N = 10) during and outside the allergy season and measured serum levels of two inflammatory cytokines (tumour necrosis factor-α and interleukin-5). Independent participants (N = 67) then sampled and rated these odours on intensity and pleasantness.

Results: While individuals with seasonal allergy had nominally more unpleasant and intense body odours during the allergy season, relative to outside the allergy season and to healthy controls, these effects were not significant. When examining immune markers, the change in perceived pleasantness of an individual's body odour (from out-to-inside pollen season) was significantly related to the change in their interleukin-5 levels but not to tumour necrosis factor-α.

Discussion: Our findings tentatively suggest that the human olfactory system could be sensitive to inflammation as present in a noncommunicable condition. Larger replications are required to determine the role of olfaction in the perception of infectious and noninfectious (e.g., chronic diseases) conditions.

The sympathetic nervous system (SNS) is a major regulatory mediator connecting the brain and the immune system that influences accordingly inflammatory processes within the entire body. In the periphery, the SNS exerts its effects mainly via its neurotransmitters norepinephrine (NE) and epinephrine (E), which are released by peripheral nerve endings in lymphatic organs and other tissues. Depending on their concentration, NE and E bind to specific α- and β-adrenergic receptor subtypes and can cause both pro- and anti-inflammatory cellular responses. The co-transmitter neuropeptide Y, adenosine triphosphate, or its metabolite adenosine are also mediators of the SNS. Local pro-inflammatory processes due to injury or pathogens lead to an activation of the SNS, which in turn induces several immunoregulatory mechanisms with either pro- or anti-inflammatory effects depending on neurotransmitter concentration or pathological context. In chronic inflammatory diseases, the activity of the SNS is persistently elevated and can trigger detrimental pathological processes. Recently, the sympathetic contribution to mild chronic inflammatory diseases like osteoarthritis (OA) has attracted growing interest. OA is a whole-joint disease and is characterized by mild chronic inflammation in the joint. In this narrative article, we summarize the underlying mechanisms behind the sympathetic influence on inflammation during OA pathogenesis. In addition, OA comorbidities also accompanied by mild chronic inflammation, such as hypertension, obesity, diabetes, and depression, will be reviewed. Finally, the potential of SNS-based therapeutic options for the treatment of OA will be discussed.

None.