https://molmed.nl/uploads/abstracts/158/il-33 discovery.pdf

IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines

Interleukin 1 (IL 1) is a polypeptide that is produced after infection, injury, or antigenic challenge. Although the macrophage is a primary source of IL 1, epidermal, epithelial, lymphoid, and vascular tissues synthesize IL 1. When IL 1 gains access to the circulation, it acts like a hormone and induces a broad spectrum of systemic changes in neurological, metabolic, hematologic, and endocrinologic systems. Some of the IL 1 that is synthesized remains associated with the plasma membrane and induces changes in local tissues without producing systemic responses. IL 1 affects mesenchymal tissue remodeling where it contributes to both destructive and repair processes. IL 1 activates lymphocytes and plays an important role in the initiation of the immune response. Receptors for IL 1 have been identified, but receptors are scarce and their affinities often do not match the potency of the biological response. The most consistent property of IL 1 is up-regulation of cellular metabolism and increased expression of several genes coding for biologically active molecules. IL 1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites. IL 1 also acts synergistically with other cytokines, particularly tumor necrosis factor. The multitude of biological responses to IL 1 is an example of the rapid adaptive changes that take place to increase the host's defensive mechanisms.

Biology of interleukin 1.

Cytokines constitute a significant portion of the immuno- and neuromodulatory messengers that can be released by activated microglia. By virtue of potent effects on resident and invading cells, microglial cyto- and chemokines regulate innate defense mechanisms, help the initiation and influence the type of immune responses, participate in the recruitment of leukocytes to the CNS, and support attempts of tissue repair and recovery. Microglia can also receive cyto- and chemokine signals as part of auto- and paracrine communications with astrocytes, neurons, the endothelium, and leukocyte infiltrates. Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context. In principle, microglial activation aims at CNS protection. However, failed microglial engagement due to excessive or sustained activation could significantly contribute to acute and chronic neuropathologies. Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions as they are sensitive to cytokine signaling.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/glia.10161

Microglia as a source and target of cytokines.

Ameboid microglia are isolated from the cerebral tissue of neonatal rat by selective cell adhesion to plastic Histochemical markers show that the microglial preparations are homogeneous (95 +/- 3%) and represent a 10% yield from starting cultures Isolated ameboid microglia contain nonspecific esterase activity, the macrophage surface antigens MAC-1 and MAC-3, and acetylated low-density lipoprotein receptors Ameboid cells have functional properties similar to those of macrophages, including the ability to engulf 5 micron latex beads, to secrete Interleukin-1 (IL-1) and to release superoxide anion Unlike monocytes and adherent spleen cells, ameboid microglia do not show peroxidase activity by histochemical stain Unlike resident peritoneal macrophages, ameboid microglia proliferate in vitro Scanning electron microscopy shows that ameboid cells have short, spinous processes that can be distinguished from the ruffled surfaces of body macrophages Our observations suggest that ameboid microglia are a distinct class of mononuclear phagocytic cells Retinoic acid and dimethyl sulfoxide, agents known to accelerate differentiation in vitro, stimulate ameboid cells to develop thin processes several hundred microns in length These “process-bearing” microglia eventually lose the capacity to engulf latex beads and to proliferate They also show reductions in nonspecific esterase activity and in the binding of acetylated low- density lipoprotein We suggest that in vitro ameboid microglia differentiate into nonphagocytic cells similar to ramified microglia found in normal adult brain The isolation techniques described here provide the opportunity to study the composition and function of different microglial subpopulations during the development of the CNS

https://www.jneurosci.org/content/jneuro/6/8/2163.full.pdf

Characterization of ameboid microglia isolated from developing mammalian brain

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertrigly-ceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system’s response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as α-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, α-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to -negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acutephase response.

/pdf/niddm-as-a-disease-of-the-innate-immune-system-association-5a7anygo5k.pdf

NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X.

Interleukin-1. A new mediator in dermatology.

A science and biotechnics continue to develop, more and more causative agents to malignant diseases are revealed. One of the most exciting discoveries is the relationship betv '̂een a retrovirus and a malignancy striking the OKT4 (T4) positive helper lymphocyte; aduit T-cell leukemia/lymphoma (ATL). Retroviruses are 100-nm single-stranded RNA viruses with an outer envelope and an inner core. The most outstanding difference between retroviruses and other RNA viruses is the retroviral possessing of a special DNA polymerase, designated reverse transcriptase. This enzyme enables the virus to replicate through a DNA template and to be integrated into the host cell DNA. The virus DNA is then passed to the daughter cells and infection remains lifelong. Retroviruses can be classified in several ways: by their genomic structure, by their appearance in the electron microscope, and by the diseases they cause. The most common way to classify retroviruses today is by their genomic structure. There are three subgroups oif retroviruses:

Retroviruses in dermatology.

Syndromic testing for lower respiratory tract infections with BioFire® FilmArray® Pneumonia Panel Plus (BF) detects 27 pathogens with a turn‐around‐time of one hour. We compared the performance of BF with culture. Samples from 298 hospitalized patients with suspected pneumonia routinely sent for culture were also analyzed using BF. Retrospectively, patients were clinically categorized as having “pneumonia” or “no pneumonia.” BF and culture were compared by analytical performance, which was evaluated by pathogen concordance, and by clinical performance by comparing pathogen detections in patients with and without pneumonia. The BF results for viruses and atypical bacteria were not included in the performance analysis. In 298 patient samples, BF and culture detected 285 and 142 potential pathogens, respectively. Positive percent agreement (PPA) was 88% (125/142). In patients with community‐acquired pneumonia (CAP), clinical sensitivity was 70% and 51%, and specificity was 43% and 71% for BF and culture, respectively. In patients with hospital‐acquired pneumonia, the corresponding numbers were 55% and 23%, and 47% and 68%. There was no significant improvement of performance, when only high‐quality sputum samples were considered. Efficacy of both BF and culture was low. Both tests are best used in CAP patients for whom the diagnosis has already been clinically established. Indiscriminate use may be clinically misleading and a cause of improper use of antibiotics.

Performance of PCR‐based syndromic testing compared to bacterial culture in patients with suspected pneumonia applying microscopy for quality assessment

http://www.clinicalmicrobiologyandinfection.com/article/S1198743X23001982/pdf

Gorm Lisby

Papers

Interleukin-1. A new mediator in dermatology.

Retroviruses in dermatology.

Performance of PCR‐based syndromic testing compared to bacterial culture in patients with suspected pneumonia applying microscopy for quality assessment

Viral epidemic preparedness: A perspective from 5 clinical microbiology laboratory in Europe