TOPIC: Inflamation Studies, and Information

[John A. Casler]

Inflamation is a critical problem as we age, and is thought by many to be the cause (or a symptom) of almost ALL age related diseases.

Below I will post (and you can too) various bits of information to this topic.

[John A. Casler]

The below from Jamie Carruthers may be of interest:

InflammationUrsula Weiss1

Nature 454, 427 (24 July 2008) | doi:10.1038/454427a; Published
online 23 July 2008

Inflammation is the body's immediate response to damage to its
tissues and cells by pathogens, noxious stimuli such as chemicals, or
physical injury. Acute inflammation is a short-term response that
usually results in healing: leukocytes infiltrate the damaged region,
removing the stimulus and repairing the tissue. Chronic inflammation,
by contrast, is a prolonged, dysregulated and maladaptive response
that involves active inflammation, tissue destruction and attempts at
tissue repair. Such persistent inflammation is associated with many
chronic human conditions and diseases, including allergy,
atherosclerosis, cancer, arthritis and autoimmune diseases.

The processes by which acute inflammation is initiated and develops
are well defined, but much less is known about the causes of chronic
inflammation and the associated molecular and cellular pathways. This
Insight highlights recent advances in our knowledge of the exogenous
and endogenous inducers of chronic inflammation, as well as the
inflammatory mediators and cells that are involved. We hope that
these articles will contribute to a better understanding of
inflammatory responses, and ultimately result in the design of more
effective therapies for the numerous debilitating diseases with a
chronic inflammatory component.

===============================

Nature 454, 428-435 (24 July 2008) | doi:10.1038/nature07201;
Published online 23 July 2008


Origin and physiological roles of inflammation
Ruslan Medzhitov1

Top of pageAbstractInflammation underlies a wide variety of
physiological and pathological processes. Although the pathological
aspects of many types of inflammation are well appreciated, their
physiological functions are mostly unknown. The classic instigators
of inflammation - infection and tissue injury - are at one end of a
large range of adverse conditions that induce inflammation, and they
trigger the recruitment of leukocytes and plasma proteins to the
affected tissue site. Tissue stress or malfunction similarly induces
an adaptive response, which is referred to here as para-inflammation.
This response relies mainly on tissue-resident macrophages and is
intermediate between the basal homeostatic state and a classic
inflammatory response. Para-inflammation is probably responsible for
the chronic inflammatory conditions that are associated with modern
human diseases.

================
Jamie Carruthers
Wakefield, UK

[carruthersjam]

64.233.167.104/search?q=cache:e0fKonJ3wswJ:www.nia.nih.gov/ResearchInformation/ConferencesAndMeetings/NIA%2BWorkshoponInflammation.htm+inflammation+aging&hl=en&ct=clnk&cd=3&gl=us&client=firefox-a

Inflammatory processes, particularly those mediating chronic inflammation, have been implicated as predictors or initiators of, or contributors to, chronic diseases and conditions of aging including cardiovascular disease, osteoarthritis, osteoporosis, Alzheimer's disease, insulin resistance and diabetes, muscle wasting, and frailty. However, the underlying biology connecting mediators of inflammation with these various disease processes is unclear. Altered cytokine profiles due to aging of the innate immune system and/or of non-immune cell types, and/or to age-related in body composition and other factors, have been proposed to contribute to age-related changes in the structure and function of tissues, pathophysiologic changes, and the development of chronic diseases of aging. Inflammatory cytokines and other mediators of inflammation can also be strong near-term predictors of mortality associated with age-related chronic diseases.

The National Institute on Aging (NIA) held a multidisciplinary Workshop on Inflammation, Inflammatory Mediators, and Aging on September 1-2, 2004 (1) to explore the current state of knowledge on the role of inflammation on aging and in the development of many chronic diseases of aging, (2) identify gaps in understanding, and (3) pinpoint opportunities for future research. The Workshop was jointly organized by the Geriatrics and Clinical Gerontology Program, the Biology of Aging Program, the Neuroscience and Neuropsychology of Aging Program, and the Intramural Research Program. The workshop participants included basic research scientists, clinical researchers, epidemiologists, and investigators in geriatrics, immunology, coagulation, cardiovascular and periodontal diseases, adiposity, musculoskeletal (osteoporosis, osteoarthritis) disorders, Alzheimer's disease, psychiatry and stress responses. State-of-the-art presentations focused on the basic biology of inflammatory mechanisms, integrative physiology, mediators of inflammation as risk factors in morbidity and mortality, and implications of interventions that modulate cytokine action. Topics included a review of age-related changes in innate and adaptive immunity, the relationships between mediators of inflammation and various age-related chronic diseases, and functional overlaps between inflammation and metabolic regulation. Other presentations highlighted inflammatory processes relating to periodontal disease, stress and depression, the protective effect of exercise and/or caloric restriction, and latent infections. A final presentation provided an overview of the lessons learned from medical intervention studies.

This document -- “NIA Workshop on Inflammation, Inflammatory Mediators and Aging: Workshop Summary” provides synopses of the various presentations and related discussion sessions. Inflammation has been classically described as an acute process characterized by heat, pain, swelling, and redness. Yet inflammation involves a wide variety of processes or mechanisms including those related to traditional inflammatory reactions, immunity, complement activation, and coagulation, as well as some processes previously described as metabolic or endocrine, such as those involved in glucose and cholesterol metabolism.

These processes are indicated or detectable through examination of biomarkers, including cytokines and acute-phase proteins. Recent research suggests that the expression of these markers can indicate underlying physiological responses in a graded and continuous manner.

The effect of aging on immunity and inflammatory processes is not well understood. Age-related changes in the levels of many pro- and anti-inflammatory cytokines have been documented, but the cause or source of this altered cytokine production has not been clearly identified. The inflammation hypothesis of aging proposes that acute inflammation, which involves a number of feedback mechanisms regulating homeostasis, confers necessary short-term benefits at the expense of accumulating long-term damage. In this scenario, structural damage accumulates from repeated episodes of acute inflammation until a threshold is crossed and function (altered production, metabolism, etc. of acute phase reactants) is affected. Thus, the injury itself may be less of a problem than the body’s response to that injury. One proposed mechanism for aging-related changes in inflammatory responses involves changes in responses mediated by T helper cells – a shift from a TH1 cytokine response, which promotes cellular immunity, to a TH2 cytokine response, which promotes humoral immunity. Another possible hypothesis is based on a change in the frequency or function of immune system cell subtypes. Although several studies have reported age-related changes in the function of T cells and B cells, it is not known how monocytes/macrophages, dendritic cells, neutrophils, natural killer (NK) cells, and NKT cells are affected. Furthermore, it is not clear whether there are intrinsic factors leading to age-dependent changes in these cell types or whether the aged tissue environment produces factors that contribute to those changes. In addition to the contributions from the immune system, recent studies in obesity have identified adipose tissue as a dynamic endocrine tissue that secretes a number of factors that contribute to systemic and vascular inflammation. Studies on the role of adiposity in insulin resistance and type II diabetes have revealed abnormal inflammatory cytokine production in adipocytes, supporting the hypothesis of an inflammatory basis for these metabolic diseases. Other factors that change with age, such as physical activity, have been associated with differing levels of inflammatory mediators. Although strong correlations have been shown between inflammatory markers and independent risk factors for disease, the associations between these markers and direct measures of disease are moderate at best.

Whether inflammatory mediators represent independent risk factors fordisease or simply mark the underlying process is not known. What is known is that adverse age-related health outcomes usually occur later in life, but the biology leading to these events begins much earlier. The key, then, is to identify earlier phenomena, to determine the overall effects of modulating the activity of inflammatory mediators such as cytokines, and to use this knowledge to develop targeted