Neuro-Immuno-Psychological Aspects of Chronic Urticaria.

Urticaria is a condition characterized by the development of itchy wheals (hives), angioedema, or both. The pathophysiology of chronic spontaneous urticaria (CSU) is still poorly understood. It is suggested that there is no dominant and independent mechanism of CSU; however, there are different immunological and non-immunological abnormalities that act simultaneously or/and follow each other resulting in clinical symptoms. The latest hypothesis points out that mast cells (MCs) to be activated via autoantibodies in autoallergic or autoimmune mechanism mediators released from degranulated MCs are responsible for the vasoactive and neurospecific effect in CSU. According to many clinical observations, it is suggested that psychological stress can be both a triggering factor in the onset of CSU and a modulating one in the course of the disease and therapy effectiveness. Of importance, the mechanistic background of the psychological stress response in the skin has not yet been fully elucidated. However, of note, a variety of inflammatory mediators, neuropeptides, and neurotransmitters facilitate this phenomenon. This review presents recent findings on the neuro-immuno-psychological aspects of CSU, highlighting an emerging role of neuro-immune interactions. It also points out the usefulness of psychological tools employment for the baseline diagnosis of perceived stress level and the presence of its symptoms. Furthermore, it proposes the implementation of non-invasive interventions to reduce psychological stress and anxiety. A bio-psycho-social approach including psychological support and patient education seems to be as important as traditional pharmacotherapy for CSU. It facilitates the effective control of active disease and a prolonged remission time in this disease.

IgE by itself affects mature rat mast cell preformed and de novo-synthesized mediator release and amplifies mast cell migratory response.

BACKGROUND: Immunoglobulin E (IgE) binds to high affinity receptor FcεRI numerously expressed on mast cells. Recent findings have revealed that IgE by itself may regulate various aspects of mast cell biology, however, detailed data is still limited. METHODOLOGY/FINDINGS: Here, we have examined the influence of IgE alone, used at different concentrations, on mast cell activity and releasability. For the study we have employed in vivo differentiated mature tissue mast cells isolated from rat peritoneal cavity. Mast cells were exposed to IgE alone and then the release of preformed and de novo-synthesized mediators, surface FcεRI expression and mast cell migratory response were assessed. IgE by itself was found to up-regulate FcεRI expression and activate mast cells to degranulation, as well as de novo synthesis and release of cysteinyl leukotrienes and TNF. We have provided evidence that IgE alone also amplified spontaneous and CCL5- or TNF-induced migration of mast cells. Importantly, IgE was effective only at concentrations ≥ 3 µg/mL. A molecular basis investigation using an array of specific inhibitors showed that Src kinases, PLC/PLA2, MAP kinases (ERK and p38) and PI3K were entirely or partially involved in IgE-induced mast cell response. Furthermore, IgE alone stimulated the phosphorylation of MAP kinases and PI3K in rat mast cells. CONCLUSION: Our results clearly demonstrated that IgE by itself, at higher concentrations, influences mast cell activity and releasability. As there are different conditions when the IgE level is raised it might be supposed that in vivo IgE is one of the important factors modulating mast cell biology within tissues.

[Bacteria and viruses modulate FcεRI-dependent mast cell activity]. / Bakterie i wirusy moduluja FcεRI-zalezna aktywnosc komórek tucznych.

Undoubtedly, mast cells play a central role in allergic processes. Specific allergen cross-linking of IgE bound to the high affinity receptors (FcεRI) on the mast cell surface leads to the release of preformed mediators and newly synthesized mediators, i.e. metabolites of arachidonic acid and cytokines. More and more data indicate that bacteria and viruses can influence FcεRI-dependent mast cell activation. Some bacterial and viral components can reduce the surface expression of FcεRI. There are also findings that ligation of Toll-like receptors (TLRs) by bacterial or viral antigens can affect IgE-dependent mast cell degranulation and preformed mediator release as well as eicosanoid production. The synergistic interaction of TLR ligands and allergen can also modify cytokine synthesis by mast cells stimulated via FcεRI. Moreover, data suggest that specific IgE for bacterial or viral antigens can influence mast cell activity. What is more, some bacterial and viral components or some endogenous proteins produced during viral infection can act as superantigens by interacting with the VH3 domain of IgE. All these observations indicate that bacterial and viral infections modify the course of allergic diseases by affecting FcεRI-dependent mast cell activation.