Interleukins (ILs), a fascinating family of cytokines. Part II: ILs from IL-20 to IL-38.

Every nucleated cell can produce and respond to cytokines, extracellular proteic/glycoproteic mediators that constitute a complex, interconnected, and flexible signaling network, addressed to modulate cell behavior and homeostasis through the interaction with high-affinity surface receptors. These messenger molecules, whose main characteristics are potency, pleiotropism, and redundancy, primarily act in autocrine, paracrine, and juxtacrine way, but can also display systemic activity in endocrine-like modality. They are generally classified according to their cellular sources, three-dimensional structure, or biological functions.

Epigenetics in autoimmune connective tissue diseases.

Unlabelled: Background. Autoimmune connective tissue diseases (ACTDs) encompass a heterogeneous group of chronic immune-mediated inflammatory disorders, primarily affecting connective tissues and clinically characterized by variable multisystem manifestations, frequently overlapping. Environmental factors are thought to promote ACTD development in genetic predisposing/endocrine permissive background through the induction of epigenetic modifications, consisting of stable, heritable, but potentially reversible changes in gene expression, occurring without alterations of the DNA sequence.

Interleukins (ILs), a fascinating family of cytokines. Part I: ILs from IL-1 to IL-19.

Every nucleated cell can produce and respond to cytokines, extracellular proteic/glycoproteic mediators that constitute a complex, interconnected, and flexible signaling network, addressed to modulate cell behavior and homeostasis through the interaction with high-affinity surface receptors. These messenger molecules, whose main characteristics are potency, pleiotropism, and redundancy, primarily act in autocrine, paracrine, and juxtacrine way, but can also display systemic activity in endocrine-like modality. They are generally classified according to their cellular sources, three-dimensional structure, or biological functions.

Focus on adipokines.

Once considered a passive reservoir for lipid storage and an inert provider of thermal/mechanical insulation, white adipose tissue (WAT) is presently seen as a highly dynamic endocrine organ that actively modulates a variety of physiologic processes, including energy balance, food intake, inflammation, immunity, metabolism, as well as cardio-vascular (CV) and neuroendocrine homeostasis. Actually, other than fatty acids and lipid moieties, WAT secretes a wide range of bioactive factors, considerably different in therms of structure and functions, including cytokines, chemokines, growth factors, complement system molecules, acute phase reactants, and hormones, among which the products predominantly or exclusively synthesized by and released from adipocytes are categorized as "adipokines". The adipokine expression is intimately linked to various parameters of adiposity (such as total body fat, percentage of body fat, and fat distribution), resulting generally (with very few exceptions, such as adiponectin, omentin, and Zinc-alpha2-glycoprotein) in positive correlation with WAT mass.

Cognition: neurobiological correlates and dynamics.

Human brain constructs knowledge, elaborates thought and promotes goal-directed behavior, organizing memories of past experience and information from the environment, perceived by senses. Cognition entails all these mental processes. Neuroscience has attempted to explore the architecture of cognition, whose neurobiological substrates are provided by widely distributed neural networks, interacting through complex connections, including sensory-fugal (inward or forward) and sensory-petal (outward or backward) projections, running in opposite direction.

Psychiatric and neuropsychological manifestations of systemic lupus erythematosus.

Background And Aim: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which may involve any organ and system, including peripheral, autonomic, and central nervous system (CNS). According to the American College of Rheumatology nomenclature, the term "neuropsychiatric SLE" identifies neurological and psychiatric syndromes occurring in patients at any time, not attributable to other causes, and categorized in three main groups, namely neurological syndromes of CNS, neurological syndromes of peripheral nervous system, and diffuse psychiatric/neuropsychological syndromes. The SLE neurological and psychiatric manifestations are usually reported together, and specific data on SLE psychopathology are limited.

The neurobiology of the human memory.

Memory can be defined as the ability to acquire, process, store, and retrieve information. Memory is indispensable for learning, adaptation, and survival of every living organism. In humans, the remembering process has acquired great flexibility and complexity, reaching close links with other mental functions, such as thinking and emotions.

Proteasomes and immunoproteasomes.

In eukaryotic cells, the protein degradation is a highly regulated and selective process. Membrane-associated or extracellular proteins are degraded in lysosomes, whereas intracellular protein dismantling is primarily non-lysosomal, being realized by complex, not-membrane enclosed and energy-dependent effectors, the proteasomes, localized in both cytoplasm and nucleus. In mammals, the proteasomes constitute a structurally and functionally heterogeneous system, with shared general architecture, different molecular compositions and functions, and tissue-specific distribution.

Focus on human natural killer cells.

Human natural killer (NK) lymphocytes were originally identified by their large granular morphology and their ability to "naturally" kill virus-infected and malignant cells without any priming. Lacking the surface markers of either B or T cells, they constitute the third major lymphocytic population, representing 5-15% of circulating lymphocytes. Their functions are tightly regulated by a delicate balance of signals transmitted by at least four different families of germ-line encoded, non-rearranged activating/inhibitory receptors.

Central nervous system effects of natural and synthetic glucocorticoids.

Natural glucocorticoids (NGC) physiologically modulate body homeostasis and coordinate adaptive responses to stress, involving almost all organs and tissues, including brain. Since their therapeutic availability, synthetic GC (SGC) have been successfully prescribed for a variety of diseases. Mounting evidence, however, demonstrated pleiotropic adverse effects (AE), including central nervous system (CNS) disturbances, which are often misdiagnosed or underestimated.

The effector T helper cell triade.

T lymphocytes play crucial role in immune responses. Effector T helper (Th) cells derive from progenitor naïve CD4+ T cells, after maturational process induced by antigenic stimulation. Their commitment depends on complex interactions with antigen-presenting cells in a permissive milieu, including antigenic type and load, costimulatory molecules and cytokine signaling.

Atherogenesis in rheumatoid arthritis: the "rheumatoid vasculopathy"?

Background And Aim: Rheumatoid Arthritis (RA) is associated with accelerated atherogenesis. RA patients have a reduced life expectancy compared to the general population, and cardiovascular (CV) disease (CVD) is recognized as a strong contributor to the excess of morbidity and mortality. Our aim was to review and discuss the recent advances in the knowledge of the RA-associated atherogenesis.

The inflammasomes: the key regulators of inflammation.

Following any threat to tissutal integrity, innate immune system promptly recognizes foreign/damage-associated molecules and orchestrates the global immune response, inducing inflammation, chemotaxis, phagocytosis and production of antimicrobial effector molecules, as well as providing instruction to the adaptive immune system. Innate immune cells detect both exogenous and endogenous danger signals through invariant germline-encoded pattern recognition receptors, including Toll-like receptors, retinoic acid-inducible gene I-like receptors, and nucleotide binding domain and leucine reach repeat containing receptors (NLRs). The recruitment of NLRs, namely IPAF, NAIPs and NALPs, by various potentially harmful stimuli leads to the assembly of inflammasomes, multimeric caspase-activating complexes entailing the sensor NLR, intracellular adaptor proteins, and procaspase-1 and -5.

The immunosenescence.

Aging is a post-maturational process, biologically characterized by the progressive failure to maintain or restore the physiologic homeostasis. Such a complex phenomenon is influenced by the interaction among genetic, epigenetic, environmental, behavioral and socio-economic factors and involves the whole body, including immune system. The age-related immune system changes, collectively termed immunosenescence and historically defined as a state of immunodeficiency, actually represent a complex remodeling that entails the increase of some immune functions and the decrease or invariability of others.

Glucocorticoids and brain functions.

Natural glucocorticoids are essential components of the body neuroendocrine system, modulating the physiological homeostasis and coordinating the adaptive responses to stressors. The complex activity of glucocorticoids involves almost all organs and tissues, including brain. Their effects on central nervous system vary with species, gender, age, hormone concentrations, timing, and duration of exposure.

Life-or-death fate in the adaptive immune system.

The tissue homeostasis is essentially realized through a precise control of cellular proliferation and death. The constant balance between expansion and contraction of different cell populations is a critical hallmark of the mammalian adaptive immune system. Immune-competent cells have to confront the survival-or-demise dilemma in primis during ontogenesis and, thereafter, in their mature life in order to maintain homeostasis, since the cellular proliferation occurring during the immune response must be counterbalanced by programmed death as the immune reaction attenuates.

Fibromyalgia and psychiatric disorders.

Fibromyalgia (FM) is a common and polymorphic syndrome, characterized by long-lasting, widespread musculoskeletal pain, in the presence of 11 or more tender points located at specific anatomical sites. A heterogeneous series of disturbances, mainly involving autonomic, neuroendocrine and neuropsychic systems, is usually present. Even if subjective, the chronic psychophysical suffering state of FM adversely affects the patient's quality of life, performance and mood.

Many ways to die: passive and active cell death styles.

In multicellular organisms, cells may undergo passive, pathological death in response to various environmental injuries, or actively decide to self-destroy in order to ensure proper physiological morphogenesis, preserve tissue homeostasis and eliminate abnormal cells. While the passive cell demise occurs in an accidental, violent and chaotic way, corresponding to "necrosis", the active auto-elimination, defined "programmed cell death" (PCD), is executed in planned modalities. Different PCD pathways have been described, such as apoptosis, autophagic death, para-apoptosis and programmed necrosis.

Carnitine: a therapeutic option for childhood psoriatic onycho-pachydermo-periostitis (POPP).

Psoriatic onycho-pachydermo-periostitis (POPP)is a rare subset of psoriatic arthritis, characterized by onychopathy, painful thickening of the periungual soft tissues, and radiological features consisting of an exuberant periosteal reaction of the terminal phalanx. The POPP treatment is debated, and side effect risk of therapies may not be offset by their benefits. We report on a successful treatment with carnitine in a 15-year old boy suffering from POPP.

Steroid-reversible parkinsonism as presentation of polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is an inflammatory disorder typically affecting elderly people, characterized by pain and stiffness in the neck and in the shoulder and pelvic girdless with prompt clinical response to low doses of corticosteroids. PMR is closely related to giant cell arteritis (GCA), likely sustained by a "subclinical vasculitis". Whereas in GCA both the central and peripheral nervous systems may be involved, only a PMR case of global, steroid-reversible dementia has been hitherto described.

OPG/RANKL system imbalance in a case of hepatitis C-associated osteosclerosis: the pathogenetic key?

Hepatitis C-associated osteosclerosis (HCAO) is an impressive example of acquired diffuse osteosclerosis in adults, recently described in ten patients infected with hepatitis C virus (HCV). Its hallmark is a painful and generalized increase of bone mass. Bone biopsies show enhanced accretion rate, usually without histological abnormalities.

Autoinflammatory diseases: the hereditary periodic fever syndromes.

Human autoinflammatory diseases (HAIDs) are a heterogeneous group of genetically determined affections characterized by seemingly unprovoked inflammation, in the absence of autoimmune or infective causes. The hereditary periodic fever syndromes (HPFSs) are a HAID subset consisting of three main nosologic entities: familial Mediterranean fever (FMF), hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), and tumor necrosis factor receptor superfamily 1A-associated periodic syndrome (TRAPS). FMF and HIDS are autosomal recessive diseases, while TRAPS is dominantly inherited.