Download Inflammation: Immune Protection or Harmful

Dr. Mary T. Weis
972.881.5725
[email protected]
Study Grant Proposal
Rationale:
The immune system is one of three major homeostatic controls for body balance.
The key to coordinate activities between the nervous, endocrine, and immune systems is
cellular communication. The immune system uses a group of chemical mediators to
communicate to and between various body cells. There are many types of cytokines and
they are grouped based on their source type or processes controlled. For a healthy
balance, negative feedback is usually necessary to make proper adjustments. During
injury to any body cell will result in a non specific inflammatory response which releases
additional chemicals that work in a positive feedback cycle which continues until it is
somehow turned off. Controlling the amount and type of chemicals is important to
prevent continued destruction of cells without a continued injury stimulus. Inability to
control immune chemical signals can lead to serious imbalances in homeostasis and
potentially create debilitating diseases.
Discussion:
Depending on the site of injury and the nature of the invader, the immune reaction
will differ. Nonspecific and specific immune cells will migrate to the injured area,
become activated, and begin their task of destroying the pathogen. Chemical messengers
produced by white blood cells are known as cell derived mediators and include various
types of prostaglandins, leukotrienes, cytokines, PAF, histamine, and kinins. The second
type of chemical signals relate to plasma derived mediators which include complement
and interferon.
While some of the acute functions of these chemicals have been studied, the
underlying initial result of these chemicals during inflammatory response creates a
clinical picture of a painful, red, swollen, and warm area. Since this response should only
last as long as the disease causing organism exists, once this occurs, the injured area
should return to normal function. The actual process by which this happens is only now
being understood. The key element seems to be a phenomenon called apoptosis or
programmed cell death. There are two theories about this process: that the cells receive
some type of “death signal” or else they do not receive the “stay-alive signal.” If the
inflammatory response continues over a longer period of time than is necessary, then
chronic inflammation may develop and can potentially create further problems.
In the last 2-3 years, more immune chemicals have been discovered and their
actions for body defenses are still being researched. Drug companies respond to this
research by creating treatments that enhance or block reactions to change the response
and the effects of the immune reaction. Some well-known examples of these drugs
include corticosteroids and aspirin. In addition, recent discussion and research about
inflammatory mediators has directed a rethinking of proper nutrition for dietary
requirements. This new research is now being published showing the link of chronic
inflammation to diabetes, Alzheimer’s, and even heart disease. Long term effects of
these cytokines on the body’s metabolic functions as it relates other types of chronic
diseases and certain cancers is only now being discussed.
As a scientist and teacher, I am interested in focusing on these immune chemicals
and their short and long term actions in the body. Western medicine is excellent at
treating acute injury cases, but we fall short in dealing with most of the chronic and
debilitating diseases for our human and animal patients. The immune system is
extremely complex and the more we discover, the more we realize the intricate balance of
communication for proper function.
Proposed Topic: “Inflammation: Immune Protection or Harmful Process?”
Questions to be explored:
a)
b)
c)
d)
What are the currently known acute functions of inflammatory mediators?
What are the possible chronic effects of these inflammatory mediators?
Which diseases or conditions have an initial inflammatory component?
What are the latest diagnostic tests to determine beneficial or harmful
chemical mediators of the immune system?
e) What are the current therapies (drugs, nutrition, and alternative) related to
controlling cytokines and promoting long term health?
Since this information will involve the most recent, cutting edge research, I will start in
the mid spring through early summer by reviewing current and recently published
literature. During summer II, my study grant will involve reading and compiling updates
on immunology, inflammation, and related cytokines using selected textbooks, medical
journals, and related medical websites based on the plan below. The list of current texts
and journals in the work plan are examples of the types of information I will be collecting
prior to analyzing the latest information. I fully expect that my literature review will
continue to expand to include additional lists of texts and medical journal articles that
have the most current information available for my proposed study grant.
Summer II Weekly Work Plan
Week 1: Immunology review of current concepts and the process of inflammation in the
immune defense.
Immunology: An Introduction, Ian Tizard, 2003
The natural history of the systemic inflammatory response syndrome, MS RangelFrausto, JAMA 1995 Jan 11; 272(2): 117-123
Systemic Inflammatory Response Syndrome, Steven Burdette, E-medicine 2006
Immunological response to infection and its role in septic shock, CL Casey,
Critical Care Clinician 2000; 16:193-211
Week 2: Acute and chronic effects of inflammatory mediators
Foye’s Principles of Medicinal Chemistry, David A Williams, PhD, 2002
Pro-inflammatory-anti-inflammatory cytokine dynamics mediated by cytokinereceptor dynamics in monocytes, Seymour, R, Mathematical Medicine and
Biology 2001; 18:159-192
Differential inhibition of inflammatory cytokine release from cultured alveolar
macrophages from smokers and non-smokers, T. Dandrea, Human Experimental
Toxicology, 1997 Oct;16(10):577-588
Eicosanoids and inflammatory response, National Academy of Sciences, 2006
p53 as a suppressor of inflammatory response in mice, Elena Komarova, The
FASEB Journal 2005; 19:1030-1032
Acute –phase proteins and other systemic inflammatory responses to
inflammation, C. Gabay, NEJM 1999; 340:448-454
Cutting Edge: an endogenous pathway to systemic inflammatory response
syndrome-like reactions through Toll-like receptor, GB Johnson, J Immunology
2004; 172:20-24
Week 3: Chronic diseases with known or proposed inflammatory component and
diagnostic tests for immune chemicals related to inflammation
Inflammatory cytokine levels correlate with amyloid load in transgenic mouse
models of Alzheimer’s disease, Nikunj Patel, Journal of Neuroinflammation 2005;
2:9
Inflammatory Cytokines as Risk Factors for a First Venous Thrombosis: A
prospective Population-Based Study, Sverre Crhistiansen, PLoS medical journal
Measurement of inflammatory cytokines by multicytokine assay in tears, L.
Malvitte, British Journal of Ophthalmology, 2006; 91:29-32
Aging and Inflammation, Life Extension Foundation, 2004
Heart Disease and the inflammatory response, Wolfgang Koenig, BMJ 2000 July
22; 321(7255): 187-188
TNF-{alpha} neutralization in cytokine-driven disease: a mathematical model to
account for therapeutic success in rheumatoid arthritis but therapeutic failure in
systemic inflammatory response syndrome, M. Jit, Rheumatology, 2005; 44: 323331
The inflammatory response: friend or enemy for muscle injury? H. Toumi, British
Journal of Sports Medicine 2003; 37:284-286
Systemic Inflammatory Response in Progression to Severe Sepsis in Critically Ill
Patients, Corianne Alberti, American Journal of Respiratory and Critical Care
Medicine 2005; Vol 171:461-468
New-onset hypertension and inflammatory response/poor outcome in acute
ischemic stroke, M.Rodriguez-Yanez, Neurology 2006; 67:1973-1978
The cellular inflammatory response in human spinal cords after injury, Jennifer
Fleming, Brain 2006; 129(12):3249-3269
Inflammatory Mediators in Gastrointestinal Defense and Injury, JL Wallace,
Experimental Biology and Medicine, 2001; 226(11): 1003-1015
Week 4: Nutritional therapies to control inflammation and drug therapies that affect
inflammation
The Inflammation Syndrome: The complete Nutritional Program to Prevent and
Reverse Heart Disease, Arthritis, Diabetes, Allergies, and Asthma, Jack Challem,
M.D., 2003
Differential Induction of Pro- and Anti- Inflammatory Cytokines in Whole Blood
by Bacteria: Effects of Antibiotic Treatment, JT Frieling, Antimicrobial Agents
and Chemotherapy, 1997; July: 1439-1443
Reduced prevalence of AD in users of NSAIDS and H2 receptor antagonists: The
Cache County Study, Anthony Breitner, Neurology 2000; 54:2066-71
Week 5: Alternative therapies that affect inflammatory chemicals and lifestyle changes
for immune health
Stop Inflammation Now! : A step-by-step Plan to Prevent, Treat, and Reverse
Inflammation, Richard M. Fleming, M.D., 2004
Systemic Inflammation and Surgery, Susan Conova, In Vivo 2002, Vol 1: Issue 2
Herbal Medicine: Expanded Commission E Monographs, Bluemthal, 2000
Positive Energy, Judith Orloff M.D., 2005
Conclusion:
Because the immune system is so important to long term health and because
immune chemicals can have all types of effects, I would like to research and review the
immune cytokines related to their short and long term affects during the inflammation
process. The immune system as an undergraduate biological subtopic is covered at
various levels of detail depending on the course. Being able to focus my studies on these
important chemicals and their functions will allow me to not only help students and
clients understand long term inflammatory effects, but to help them make decisions on
proper therapies for themselves as well as their patients and pets. As a teacher and
scientist, I will be able to have an in-depth understanding and preparedness to answer
questions and determine proper treatments for my patients at all stages of their lives.
Presentations to interested faculty, nursing students, and community health members
either face to face or via the web can be conducted.