Neuroimmune mechanisms of pruritus in atopic dermatitis

Atopic dermatitis is a chronic hereditary recurrent skin disease. One of the most pronounced symptoms of this dermatosis is itchy skin. Pruritus accompanies atopic dermatitis in more than 80% of cases. This review presents modern data on the mechanisms of pruritus formation in atopic dermatitis. The issues of etiological factors, neuroimmune interactions, peculiarities of skin dysfunction, as well as the role of stress are considered. The relevance of studying the topic is due to the high prevalence of atopic dermatitis among the population, a decrease in the quality of life and the lack of effective therapy. Analysis of the literature indicates the need for a comprehensive assessment of the pathogenetic mechanisms of the development of pruritus in atopic dermatitis. A more in-depth study of the mechanisms of neurogenic inflammation in atopic dermatitis will contribute to the development of new methods of diagnosis and treatment.

Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus

Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in Trpv4 knockout (KO) mice following treatment with AEW. The increase in the intracellular calcium levels by TSLP in the dorsal root ganglia (DRG) of Trpv4 KO mice was also significantly attenuated. The spontaneous scratching bouts were significantly decreased in both the HC067047-treated and Trpv4 KO AEW mice. Importantly, the TSLP-dependent release of tryptase from the mast cells was significantly reduced in both the HC067047-treated mice and Trpv4 KO AEW mice. Notably, inhibition of the TSLP-induced signaling pathway in DRG selectively reduced the spontaneous scratching bouts in AEW mice. Overall, the results demonstrated that the cutaneous neuroimmune interactions of TSLP and TRPV4 play pivotal roles in dry skin-induced pruritus.

The Pathology of Type 2 Inflammation-Associated Itch in Atopic Dermatitis

Accumulated evidence on type 2 inflammation-associated itch in atopic dermatitis has recently been reported. Crosstalk between the immune and nervous systems (neuroimmune interactions) is prominent in atopic dermatitis research, particularly regarding itch and inflammation. A comprehensive understanding of bidirectional neuroimmune interactions will provide insights into the pathogenesis of itch and its treatment. There is currently no agreed cure for itch in atopic dermatitis; however, increasing numbers of novel and targeted biologic agents have potential for its management and are in the advanced stages of clinical trials. In this review, we summarize and discuss advances in our understanding of type 2 inflammation-associated itch and implications for its management and treatment in patients with atopic dermatitis.

Effects of placebo administration on immune mechanisms and relationships with central endogenous opioid neurotransmission

Behavioral conditioning and expectation can have profound impact on animal and human physiology. Placebo, administered under positive expectation in clinical trials, can have potent effects on disease pathology, obscuring active medications. Emerging evidence suggests placebo-responsive neurotransmitter systems (e.g., endogenous opioid) regulate immune function by manipulating inflammatory proteins including IL-18, a potent pro-inflammatory, nociceptive cytokine implicated in pathophysiology of various diseases. Validation that neuroimmune interactions involving brain μ-opioid receptor (MOR) activity and plasma IL-18 underlie placebo analgesic expectation could have widespread clinical applications. Unfortunately, current lack of mechanistic clarity obfuscates clinical translation. To elucidate neuroimmune interactions underlying placebo analgesia, we exposed 37 healthy human volunteers to a standardized pain challenge on each of 2 days within a Positron Emission Tomography (PET) neuroimaging paradigm using the MOR selective radiotracer, 11C-Carfentanil (CFN). Each day volunteers received an intervention (placebo under analgesic expectation or no treatment), completed PET scanning, and rated their pain experience. MOR BPND parametric maps were generated from PET scans using standard methods. Results showed placebo reduced plasma IL-18 during pain (W74 = −3.7, p < 0.001), the extent correlating with reduction in pain scores. Placebo reduction in IL-18 covaried with placebo-induced endogenous opioid release in the left nucleus accumbens (T148 = 3.33; puncorr < 0.001) and left amygdala (T148 = 3.30; puncorr < 0.001). These findings are consistent with a modulating effect of placebo (under analgesic expectation in humans) on a potent nociceptive, pro-inflammatory cytokine (IL-18) and underlying relationships with endogenous opioid activity, a neurotransmitter system critically involved in pain, stress, and mood regulation.

Associative influence of new coronavirus infection SARS-CoV-2 during pregnancy on formation of neurological disorders in newborns: clinical case

The Severe Acute Respiratory Syndrome caused by Coronavirus-2 (SARS-CoV-2) has a destructive impact on the population all over the world. In this scenario, the extent, to which the disease will affect more vulnerable individuals, such as pregnant women, is a major concern. Since pregnancy can be a risk factor for respiratory viral infections, there are significant differences regarding the severity of COVID-19 between pregnant and non-pregnant women. In these circumstances, there arises a serious problem associated with the possibility of harm to the health and neuropsychiatric development of the posterity of infected mothers. The acute inflammatory response observed during the disease can lead to several types of nervous system disorders in the newborn. In the light of neuroimmune interactions on the mother-fetus hematoplacental relationship, a clinical case is described that reflects the consequences for the nervous and psychoneurological development of the newborn from SARS-CoV-2 infected mother.

Enteric neuroimmune interactions coordinate intestinal responses in health and disease

The enteric nervous system (ENS) of the gastrointestinal (GI) tract interacts with the local immune system bidirectionally. Recent publications have demonstrated that such interactions can maintain normal GI functions during homeostasis and contribute to pathological symptoms during infection and inflammation. Infection can also induce long-term changes of the ENS resulting in the development of post-infectious GI disturbances. In this review, we discuss how the ENS can regulate and be regulated by immune responses and how such interactions control whole tissue physiology. We also address the requirements for the proper regeneration of the ENS and restoration of GI function following the resolution of infection.