Rainer H Straub

University of Regensburg | UR · Department of Internal Medicine I

Background: All active scientists stand on the shoulders of giants and many other more anonymous scientists, and this is not different in our field of psycho-neuro-endocrine immunology in rheumatic diseases. Too often, the modern world of publishing forgets about the collective enterprise of scientists. Some journals advise the authors to present o...

It is explained how pain arises, how it is transmitted to the central nervous system, and finally where it arrives in the brain. In addition to acid, heat, and cold, inflammatory situations cause pain. The immune messenger substances can directly activate the pain receptors. The face, tongue, throat, hands, and feet are most densely supplied with p...

The chapter attempts to define stress, and distinguishes between acute and chronic stress. It becomes clear that acute stress can be good, but chronic stress is unhealthy. The specific examples of caregiver stress and workplace stress are examined. The principle of the double hit with two simultaneous stress events is introduced. Finally, it is sho...

The sympathetic nervous system is very important for increasing blood pressure by retaining water in the body and constricting vessels. During acute inflammation situations and in fight or flight responses, the sympathetic nervous system and the cortisol stress axis are activated simultaneously, the stress systems cooperate. This cooperation is des...

Love life consumes a lot of energy, and during this time, one consumes less food. This could also be called “anorexia of the lovers”. Therefore, it is beneficial if this energy-consuming love program similarly is switched off during an acute activation of the immune system. This shutdown program has been positively selected for acute inflammatory e...

When a stressful situation and an inflammatory situation coincide, it often leads to an amplification of inflammation. Inflammation, in turn, can affect brain function (Sickness behavior). This amplification of inflammation can be beneficial when there are acute infection problems. The mutual immediate assistance of the immune system and the brain...

The activation of the immune system, psychological stress, chronic pain, sleep problems, chronic smoldering infections, fears, smoking, etc. lead to unwanted energy expenditures. Using simple physical considerations, it is illustrated that any form of unwanted energy expenditure leads to an impairment of the desired physical/mental activity. This c...

Very similar to muscle loss, bone loss is the end result of various causes. Sickness behavior is once again at the center, as it causes immobility and loss of appetite. Since it was positively selected for short-term inflammatory reactions, it is also used again in chronic inflammations. This is accompanied by the loss of growth hormone, androgens,...

Considering that blood loss is energetically very costly, it becomes understandable that blood clotting must function well after wounds and injuries. Typical activation factors of clotting are the hormones of the sympathetic nervous system (noradrenaline, adrenaline) and immune messengers such as tumor necrosis factor (TNF) and interleukin-6. Incre...

Insulin is the body’s only storage hormone, promoting the uptake of glucose and fatty acids into the storage organs adipose tissue and muscle. In the event of acute inflammation or an acute fight or flight response, it is important to switch off the effect of insulin (inducing insulin resistance) so that the now increasingly circulating glucose mol...

The muscle contains a larger amount of available energy. During fasting, muscle proteins are used as energy-rich substrates for the first 2 days; from day 2–3 onwards, fat is primarily used. It is therefore a positively selected program for providing energy in a state of hunger. In chronic inflammations, this program is used again, and cytokines ar...

In the preceding chapters, energy expenditure through different inflammatory and psychomotor situations was presented. Now, the significance of the higher energy expenditure through the immune system (inflammation) on the one hand, and the brain/muscles (psychomotor) on the other hand, is related to the energy expenditure of young and old healthy p...

Sickness behavior is understood as the sum of various symptoms such as discomfort, daytime fatigue, exhaustion, lack of drive, increased feeling of cold, muscle pain, joint pain, loss of appetite, anxiety, depressive feelings, retreat into familiar protected loactions, and “lack of energy.” This program was positively selected for short-term inflam...

The chapter first demonstrates sleep physiology and various parameters for measuring sleep quality. On the basis of these considerations, it is shown that chronic inflammation is associated with sleep problems, which are improved after anti-inflammatory therapy. The cause of sleep problems are nocturnal pain and increased nocturnal inflammation, le...

Loss of appetite is part of the Sickness behavior or the fight-or-flight response, a positively selected program for conserving energy when an acute inflammation or an acute stressful life situation must be managed. Since foraging is energetically expensive, it is reduced to make the energy released available to the immune system or the brain/muscl...

This chapter examines the energy expenditure of the immune system in more detail. The spectrum from normal to massive inflammation is covered. It is shown that there is a continuum between normal and sepsis when looking at the cytokine interleukin-6 in the blood, for example. During the aging process, there is a very slight increase in interleukin-...

Starting from the physical definition of energy, this chapter presents its significance for the human body. Since a human being, from an energy perspective, represents an open system that absorbs energy through food and loses it again in various ways, the human body requires energy storage and controlled energy release. The main storage organs are...

In this chapter, further important conditions are mentioned that contribute to increased energy expenditure. These include sleep problems with increased wakefulness, during which one exhibits increased physical activity and therefore expends more energy. Also, there are chronic smoldering infections without a strong inflammatory response, such as c...

The brain and immune system require a lot of energy, and they are selfish because they claim this energy for themselves in case of danger, without asking anyone else. They have their own factors for this selfish allocation of energy, which are released when needed. In short-term events, the brain and immune system help each other. In long-term even...

Throughout the evolutionary history of humans, several important factors have been positively selected that can contribute to a higher body weight. Compared to great apes, this is, for example, the better energy storage in adipose tissue. In addition, energy shortages in the womb are crucial for a non-genetically determined weight gain in childhood...

With the help of evolutionary biology, founded by Charles Darwin and Alfred Russel Wallace, physicians have gradually adopted the message of the theory of evolution and created a new field of work—evolutionary medicine. This chapter briefly discusses the history and content of modern evolutionary theory. It presents the vast periods of time that ar...

Objective Soluble transferrin receptor (sTfR) is considered to be a useful biomarker for the diagnosis of iron deficiency (ID), especially in the setting of inflammation as it is thought to be not affected by inflammation. We analysed the relationship between sTfR levels and inflammatory markers in patients with known or suspected inflammatory rheu...

Introduction: Patients often go to the physician with medically unexplained symptoms (MUS). MUS can be autonomic nervous system-related “unspecific” symptoms, such as palpitations, heart rhythm alterations, temperature dysregulation (hand, feet), anxiety, or depressive manifestations, fatigue, somnolence, nausea, hyperalgesia with varying pains and...

Sleep has a homeostatic role in the regulation of the immune system and serves to constrain activation of inflammatory signalling and expression of cellular inflammation. In patients with rheumatoid arthritis (RA), a misaligned inflammatory profile induces a dysregulation of sleep-wake activity, which leads to excessive inflammation and the inducti...

Background Energy is the currency of life. The systemic and intracellular energy metabolism plays an essential role for the energy supply of the resting and activated immune system and this also applies to chronic inflammatory diseases.Objective This presentation examines both components of the systemic and cellular energy metabolism in health and...

In this review article the current model of the interaction between the sympathetic nervous system (SNS) and the immune system in the context of chronic inflammation is presented. Mechanisms in the interaction between the SNS and the immune system are shown, which are similar for all disease entities: 1) the biphasic effect of the sympathetic syste...

The immune system is embedded in a network of regulatory systems to keep homeostasis in case of an immunologic challenge. Neuroendocrine immunologic research revealed several aspects of these interactions over the past decades, e.g. between the autonomic nervous system and the immune system. This review will focus on evidence revealing the role of...

The central nervous and immune systems are often in competition for energy substrates. After infection or injury, energy expenditure typically increases while exploratory behavior and food intake decrease (sickness behavior). However, in the absence of food intake, animal bodies can only sustain increased expenditure for 3–7 weeks before energy sub...

This chapter presents important points regarding early traumatic experiences. The pioneers of trauma research and their approach to searching for childhood burdens and their consequences are briefly mentioned. Furthermore, specific questionnaires and the first large epidemiological studies are named. Depending on the time point of the child’s expos...

This chapter summarizes the follow-up problems of earlier traumatic situations. Particular weight is given to the alcohol problem, drug abuse, smoking, depression, anxiety disorder, obesity, heart attack, lung disease (e.g. asthma), gastrointestinal disorders (e.g. irritable bowel syndrome) and the chronic inflammatory situation. Large epidemiologi...

This chapter presents various possibilities for chronic activation of the immune system as a result of trauma-related brain changes. In order to transfer the central nervous system trauma sequelae to the periphery in the direction of the immune system, there are four essential links between the brain and the immune system. Direct links (No. 1) are...

Stress-associated somatic and psychiatric disorders are often linked to non-resolving low-grade inflammation, which is promoted at least in part by glucocorticoid (GC) resistance of distinct immune cell subpopulations. While the monocyte/macrophage compartment was in the focus of many clinical and preclinical studies, the role of myeloid-derived su...

Aim: We analyzed the added value of sTfR measurement in routine clinical practice to standard parameters (SP) of iron deficiency in the detection of iron deficiency anemia (IDA) in patients with rheumatoid arthritis (RA). Methods: Blood samples from 116 patients with RA were analyzed in a prospective study. Based on biochemical parameters, patie...

Background: Different parts of an organism like the gut, endocrine, nervous and immune systems constantly exchange information. Understanding the pathogenesis of various systemic chronic diseases increasingly relies on understanding how these subsystems orchestrate their activities. Methods: We started from the working hypothesis that energy is...

Purpose Recent studies demonstrated a contribution of adrenoceptors (ARs) to osteoarthritis (OA) pathogenesis. Several AR subtypes are expressed in joint tissues and the β2-AR subtype seems to play a major role during OA progression. However, the importance of β2-AR has not yet been investigated in knee OA. Therefore, we examined the development of...

Objective Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model...

Prokineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and circadian rhythms. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, the role of PK2 in the pathogenesis of rh...

Objective Interleukin-33 (IL-33) has been investigated as a mediator in the pathogenesis of fibrosis in lung, liver, and heart. There is accumulating evidence for the involvement of the IL-33/IL-33 receptor ST2L signalling pathway in systemic sclerosis (SSc). Little is known about the role of serum sST2 in SSc, which is the subject of the present i...

Exogenous adenosine and its metabolite inosine exert anti-inflammatory effects in synoviocytes of osteoarthritis (OA) and rheumatoid arthritis (RA) patients. We analyzed whether these cells are able to synthesize adenosine/inosine and which adenosine receptors (ARs) contribute to anti-inflammatory effects. The functionality of synthesizing enzymes...

Zusammenfassung Hormonelle und neuronale Signalwege können die Manifestation einer chronisch-entzündlichen Systemerkrankung entweder begünstigen oder verhindern. Bei bereits manifester Erkrankung modulieren Hormone und Neurotransmitter den Krankheitsverlauf, in dem sie die Krankheitsaktivität erhöhen oder abschwächen. Beispiele hierfür sind der ent...

Prokineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and the circadian rhythm. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, whether PK2 influences the pathogenesi...

In autoimmune rheumatic diseases, oestrogens can stimulate certain immune responses (including effects on B cells and innate immunity), but can also have dose-related anti-inflammatory effects on T cells, macrophages and other immune cells. By contrast, androgens and progesterone have predominantly immunosuppressive and anti-inflammatory effects. H...

In experimental arthritis, glucocorticoid secretion is inadequate relative to inflammation. We hypothesized that IL-1 is a key factor for inadequate glucocorticoid secretion in arthritic rats. Collagen type II—induced arthritis (CIA) in DA rats was the model to study effects of IL-1 on adrenal function. In the CIA model, an increase of intraadrenal...

Background Water retention is a typical feature of acute inflammatory episodes, chiefly implemented by the sympathetic nervous system (SNS) and the hypothalamic–pituitary–adrenal (HPA) axis. This is an important compensatory mechanism counteracting expected water loss, e.g., due to sweating. Both the SNS and HPA axis are activated in polymyalgia rh...

Introduction: In arthritic mice, a sympathetic influence is proinflammatory from the time point of immunization until the onset of disease (days 0-32), but reasons are unknown. Disruption of the major anti-inflammatory pathway through Gαs-coupled receptors probably play a role. For example, noradrenaline cannot operate via anti-inflammatory β2-adr...

Mental memory system has sensory memory, short-term memory, working memory, and long-term memory. Working memory “keeps things in mind in parallel” when performing complex tasks. Similar aspects can be found for immunological memory. However, there exists another one, the memory of the fatty acid system. This article shows sensory memory of the fat...

Bone marrow-derived mesenchymal stem cells (BMSCs) represent an alternative to chondrocytes to support cartilage regeneration in osteoarthritis (OA). The sympathetic neurotransmitter norepinephrine (NE) has been shown to inhibit their chondrogenic potential; however, their proliferation capacity under NE influence has not been studied yet. Therefor...

Mice with an overall deletion of the sensory neuropeptide α-calcitonin gene-related peptide (α-CGRP) develop an age-dependent osteopenic bone phenotype. Underlying molecular mechanisms of how αCGRP affects bone cell metabolism are not well understood. This study aims to characterize differences in metabolic parameters of osteoblast-like cells (OB)...

Objective Patients with chronic inflammatory autoimmune diseases benefit from a broad spectrum of immunosuppressive and antiproliferative medication available today. However, nearly all of these therapeutic compounds have unwanted toxic side effects. Recent knowledge about the neurobiology of placebo responses indicates that associative learning pr...

The peripheral nervous system modulates bone repair under physiological and pathophysiological conditions. Previously, we reported an essential role for sensory neuropeptide substance P (SP) and sympathetic nerve fibers (SNF) for proper fracture healing and bone structure in a murine tibial fracture model. A similar distortion of bone microarchitec...

Das immunologische Gedächtnis bietet sehr oft einen wirksamen Schutz nach erstmals durchgemachter Infektionskrankheit. Masern ist das Beispiel par excellence, da ein lebenslanger Schutz besteht. Diese Leistung, die Energieausgaben minimiert, basiert im Wesentlichen auf der Gedächtnisfunktion des Immunsystems. Nach einer kurzen Einführung zum angebo...

Defekte des Immunsystems – entweder genetisch oder durch Mikroben wie HIV-1 bedingt – haben oft eine unmittelbare Wirkung auf die Infektabwehr und auf die Ausbildung des immunologischen Gedächtnisses. Da im Immunsystem viele verschiedenen Zelltypen existieren, können sehr variable molekulare Störungen die Ursache der Problematik sein. Die Symptome...

Isolierte Störungen im Gehirn beeinflussen gezielt das mentale Gedächtnis. In diesem Kapitel werden ausgesuchte Beispiele dafür vorgestellt und die Hirnregionen werden sichtbar gemacht. Neurologen, Psychiater und Psychologen befassen sich mit diesen Themen. Dazu gehören Inselbegabung, Gesichtsblindheit und Epilepsie im Schläfenhirn, die alle Störun...

Das Immungeschehen beeinflusst indirekt über die Aktivierung der Stressachsen den Abruf von energiereichen Substraten aus dem energiespeichernden Gedächtnis. Gleichzeitig können Immunzellhormone (Zytokine) direkt an der Fettzelle den Abruf der Fettsäuren aktivieren. Immunologische Gedächtniszellen nisten sich im Fettgewebe ein und können bei einem...

Die vorausgehenden Buchteile I und II machten deutlich, wie ein einziges Gedächtnis und das Zusammenspiel von verschiedenen Gedächtnissen unter gesunden Bedingungen funktionieren. In den drei vorausgehenden Kapiteln wurden Gedächtnisstörungen und jeweilige Krankheitskonsequenzen in den drei verschiedenen Bereichen „mental“, „immunologisch“ und „ene...

Mit diesem Kapitel befinden wir uns bereits im Buchteil II, wo die normale „gesunde“ Interaktion der drei Gedächtnisse dargestellt wird. Wenn wir die Interaktion Unterhaltung nennen, ist es mehr als ein Monolog, sondern ein Zwiegespräch, vielleicht auch eine Gruppenunterhaltung, eine Dreiecksbeziehung. Der Leser stellt zu Recht folgende Fragen: 1)...

Mit markanten Beispielen wird die Bedeutung von Gedächtnis gezeigt. Dennoch sind mit Gedächtnis auch Gefahren verbunden. Gedächtnis ist meistens gut, wenn wir Flüssigkeit oder Nahrung suchen (mentales Gedächtnis), wenn eine infektiöse Kinderkrankheit zum zweiten Mal durchgemacht wird (immunologisches Gedächtnis) oder wenn wir Energie aus dem Fettge...

Ausgehend vom evolutionsbiologisch „alten“ Gedächtnis für Gerüche werden wichtige Orte im Gehirn dargestellt, die bei der Gedächtnisbildung eine entscheidende Rolle spielen. Mit diesem Vorwissen erfährt der Leser Gedächtnis par excellence aus psychologischer Perspektive, genauer aus neuropsychologischer Erfahrung heraus. Wissenschaftsgeschichtlich...

Wenn wir uns mit Essen befriedigen, nimmt das Belohnungsgedächtnis Einfluss auf das energiespeichernde Gedächtnis. Im gesteigerten Fall kann dies zur Fettsucht beitragen. Befinden wir uns dagegen in einer Bedrohungslage, brauchen wir das mentale Gedächtnis für die adäquate Reaktion. Die Nahrungsaufnahme wird blockiert und die Stressachsen aktiviert...

Das mentale Gedächtnis steuert das Immunsystem, in dem das Gehirn zum Beispiel die Hemmung des Immunsystems mittels Konditionierung erlernt (Pawlow!). Diese Methoden könnten bei Transplantierten eingesetzt werden, um die Dosis der medikamentösen Immunhemmung zu verringern. Das Plazebothema wird in diesem Zusammenhang erläutert und mit der Regulatio...

Zunächst werden der Begriff der Energie im Körper und die Regelung von Energiespeicherung und -freisetzung vorgestellt. Das Fettgewebe speichert große Mengen an freisetzbarer Energie. Das Kapitel stellt die abgespeicherten Fettmoleküle – besonders die Fettsäuren – dar. Dieser Schilderung folgen ähnlich wie beim mentalen und immunologischen Gedächtn...

Dieses Kapitel wird hier eingeschoben, um dem Leser eine kleine Plattform der Evolutionsbiologie zu liefern. Die evolutionäre Abstammung des Menschen wird als Starter benutzt. Ja, wir stammen von Affen ab. Des Weiteren werden die Eckpunkte der Evolutionstheorie aufgezeigt. Die Evolutionsmedizin wird an Beispielen verdeutlicht. Die Medizin wird durc...

Im Buchteil I wurde die Aufnahme, Konsolidierung und Langzeitabspeicherung von Fetten beschrieben. Fette werden im Darm verkleinert, in der Dünndarmzelle aufgenommen, über die Blutbahn mit (kurzkettige Fettsäuren) oder ohne (langkettige Fettsäuren) Beteiligung der Leber zum Fettgewebe transportiert und dort langfristig als Triglyzerid und als Kompl...

Warum wir schlecht gegen AIDS und Lepra gerüstet sind. Warum die posttraumatische Belastungsstörung den ganzen Körper krank macht. Warum Adipositas auf Entzündung und Stress basiert - diese und andere Fragen erhellt Rainer H. Straub anhand eines faszinierenden Modells: Es gibt mindestens drei verschiedene Formen des Gedächtnisses in unserem Körper:...

“Nothing in Biology makes sense, except in the light of evolution.” This famous citation of Theodosius Dobzhansky also underlies the integrative field of evolutionary medicine, which faces the challenge to combine (patho-)physiological mechanisms with evolutionary function. Here we introduce a concept from the study of animal behavior, which are th...

Today, inflammatory rheumatic disorders are effectively treated, but many patients still suffer from residual fatigue. This work presents pathophysiological mechanisms of fatigue. First, cytokines can interfere with neurotransmitter release at the preterminal ending. Second, a long-term increase in serum concentrations of proinflammatory cytokines...

While patients with rheumatoid arthritis (RA) sometimes demonstrate thyroidal illness, the role of thyroid hormones in inflamed synovial tissue is unknown. This is relevant because thyroid hormones stimulate immunity, and local cells can regulate thyroid hormone levels by deiodinases (DIO). The study followed the hypothesis that elements of a thyro...

In recent years, first evidences emerged that sympathetic neurotransmitters influence osteoarthritis (OA) manifestation. Joint-resident stem cells might contribute to cartilage repair, however, their chondrogenic function is reduced. The neurotransmitter norepinephrine (NE) was detected in the synovial fluid of trauma and OA patients. Therefore, th...

Nociceptive sensory nerve fibers have never been investigated in the ligamentum flavum (LF) of patients with LSS. The aim was to analyze nociceptive sensory nerve fibers in the ligamentum flavum (LF) of patients with LSS. A prospective study in patients with lumbar spinal stenosis (LSS) undergoing invasive surgical treatment for lumbar spinal steno...

Sympathetic nerve fibers and NE are present in healthy and osteoarthritic (OA) synovial tissue and fluid. The potential regenerative role of progenitors in cartilage has been confirmed, though, in OA, these cells exhibit reduced chondrogenic capacity. The aim of this study was to explore the role of NE on proliferation and chondrogenesis of ASCs. S...

In rheumatoid and collagen-induced arthritis (CIA) relative insufficiency of adrenal glands (AG) in later stages of the disease is known. Additionally, migration of macrophages and dendritic cells (DCs) into AG has been described. We hypothesized that these cells contribute to inadequate glucocorticoid secretion. CIA was induced in DA rats. Cytokin...

Objectives: The appearance of endogenous tyrosine hydroxylase-positive cells (TH+ cells) in collagen-induced arthritis was associated with an anti-inflammatory effect. Here we investigated putative anti-inflammatory and antinociceptive effects of the transfer of induced, bone marrow stem cell-derived TH+ cells (iTH+ cells) on murine antigen-induce...

Synovial adipose stem cells (sASC) can be differentiated into catecholamine-expressing sympathetic neuron-like cells to treat experimental arthritis. However, the pro-inflammatory tumor necrosis factor (TNF) is known to be toxic to catecholaminergic cells (see Parkinson disease), and this may prevent anti-inflammatory effects in inflamed tissue. We...