Inflammation is characterized by an influx of leukocytes into a site of infection or tissue distress which is directed by a cascade of biochemical and cell adhesion events. Inflammation is a natural process which results from your body’s immune defense against pathogens such as bacterial and viruses. Symptoms can include swelling, joint pain, and redness.

Sometimes the body’s defense system (immune system) inappropriately triggers an inflammatory response when there are no foreign substances to fight off. In these diseases, called autoimmune diseases, the body’s normally protective immune system causes damage to its own tissues. The body responds as if normal tissues are infected or somehow abnormal.

Inflammatory diseases refer to diseases that are caused or contributed to by a complicated set of functional and cellular adjustments involving acute or chronic changes in microcirculation, movement of fluids, and influx and activation of inflammatory cells (e.g., leukocytes) and complement, and included autoimmune diseases. Examples include reperfusion injury, ishemia injury, strock, transplant rejection, hepatitis, thyroiditis periodontal disease, arthritis, psoriasis, multiple sclerosis and sepsis.

Inflammation of the central nervous system (CNS) (neuroinflammation) is now recognized to be a feature of all neurological disorders. In multiple sclerosis, there is prominent infiltration of various leukocyte subsets into the CNS. Even when there is no significant inflammatory infiltrates, such as in Parkinson or Alzheimer disease, there is intense activation of microglia with resultant elevation of many inflammatory mediators within the CNS.

Specific Types of Diseases

Alpha-gal syndrome (AGS): is an emerging tick bite-associated immunoglobulin E-mediated allergic condition characterized by reaction to the oligosaccharide galacose-alpha-1,3-galactose (alpha-gal) which is found in mammalin meat and products derived form mammals, including milk and other diary products. Symptoms range from mild (e.g., rash or gastrointestinal upset) to severe (anaphylaxis). Onset typically occurs 2 or mroe hours after exposrue to alpha-gal. No treatment is currently available. Evidence suggests that the reaction is primarily associated with the bite of the lone star tick (Ambylomma americanum) in the United States with cases most prevalent in the sourthern, midwester and mid-Atlantic United States, overlapping the range of the lone star tick. See CDC

Meningitis: inflammation of the membranes covering the brain upon bacterial and viral infection. Most prominent in the cae of bacterial meningitis, clinical symptoms include a horrible headache, fever, malaise and pain when moving the neck.

Polyarteritis nodosa: is a disease in which sigments of medium sized arteries become inflamed and damaged, reducing the blood supply to the organs. It is often fatal if not treated adequately. It usually develops at 40-50 but can occur at any age. Men are three times more likely than women to develop it. Its cause is unknown, but reactions to some drugs and vaccines may cause it.

Polymyositis: is a chronic connective tissue disease characterized by painful inflammation and degeneration of the muscles; dermatomyositis is polymyositis accompanied by skin inflammation. These diseases result in disabling muscle weakness and deterioration. The weakness typically occurs in the shoulders and hips but can affect muscles symmetrically throught the body. Polymyositis and dermatomyositis usually occur in adults from ages 40-60 or in children from ages 5-15. Women are twice as likely as men to develop either disease. The cause is unknown although viruses or autoimmune reactions may play a role. Cancer may also trigger the diases. Symptoms, which may begin during or just after an infection, include muscle weakness (particularly in the upper arms, hips, and thighs), muscle and joint paint, Raynaud’s phenomenon, a rash, difficulty in swallowing, a fever, fatigue, and weight loss. In dermatomyositis, rashes tend to appear at the same time as periods of muscle weakness and other symtpoms.

Psoriasis: is a chronic and recurring disease recognized by its raised red silvery scaled eruptions and plaques of various siezes which can appear anywhere on the skin. The disease is common, affecting from 2-4% of the Caucasian poulation. Psoriasis is a T-cell-mediated inflammatory disease in which the activation of the immune system in focal skin regions, mediated by CD8+ and CD4+ T lymphocytes, results in epidermal hyperplasiia. The cause of psoriatic lesions has been suggested to be related to antigens/superantigens or autoantigens provided by non-dermal inducing factors (PCT/US2006/030281). No known therapeutic method can cure psoriasis, but the majority of cases can be controlled. In less severe cases, treatment with pomades or emollient creams that keep the skin hydrated can be sufficient. In many of the moderate cases of psoriasis, topical formulations (pomades, creams, gels and lotions) containing corticosteroids are used by applying them underneath an occlusive covering made of cellophane or polyehtylene, or incorporating them into an adhesive bandage. In the more severe cases, the antineoplastics methotrexate or cyclosporin, both of which provike serious side effects, can be used.

Applying a topical agent is typically the first approach to treating psoriasis. All topical steroids have anti-inflammatory, anti-pruritic and vasoconstrictive effects. Topical agents include corticosteroids, coal tar, anthralin, calcipotriene and tazarotene. Coal tar treatment involves almost a month of messy topical treatments at a day treatment center. Although this method has a high rate of success in clearing skin, it is reltaively expensive and time-consuming. Anthralin is a synthetic derivative of a tree bark extract and is a cellular antiproliferative agent that decreases the rate of epidermal cell growth. Although anthralin is considered one of the most effective agents available for treating psoriasis, it is not in widespread use because of its high potential to cause irritation and staining of the skin. Calcipotriene is a synthetic vitamin D-3 analog that regulates skin cell production. It is not in widespread use, however, because it is expensive and dosage is limited due to the risk of iritation and vitamin D toxicity. Tazarotene is a retinoid derivative but can also cause irritation.

Phototherpay can also be used for extensive, widespread disease. There are two main forms of phototherapy, UVB and PUVA phototherpay. UVB, or Ultraviolet B, phototherapy uses light having a wavelenght in the range of 290-320 nm. Such phototherpay is usually combined with one or more topical treatment including topically applying coal tar, followed by using UVB, using a coal tar bath, followed by UVB, and then followed by topically applying anthraline, or using UVB in combination with topically applying corticosteroids, calcipotriene, tazarotene, or simply bland emollients.

Sjogren’s syndrome: is a chronic inflammatory disorder characterized by excessive dryness of the eyes, mouth, and other mucous membranes. The syndrome is often associated with other symptoms more characteristic of rheumatoid arthritis of lups. The cause of Sjogren’s syndrome is not known although it is thought to be an autoimmune disease. It is less common than RA and more prevalent in women. Lympoma, a cancer of the lymphatic system, is 44 times mroe common in people who have Sjogren’s syndrome. No cure is available, but symptoms can be relieved.

Systemic Inflammatory Response Syndrome (SIRS): Several infective and non-infective causes of SIRS are recognized. Infective causes of SIRS include sepsis and spetic chock, infection caused bybacterial pathogens, viruses, fungi, and parasites. Non-infective causes of SIRS include haemorrhagic shock, acute pancreatitis, and burns. Systemic leukocyte activation (cytokine-mediated) is a direct consequence of SIRS and if excessive, can lead to MODS and multiple organ failure. As a consequence of overactive SIRS response, leukocytes become activated within the general circulation and some then lodge within the pulmonary microcirculation. As the condition develops, leukocytes migrate into the pulmonary interstitium and increased endothelia permeability leads to tissue oedema. The leukocytes in the lungs both respond and contribute to the infalmmatory process in ARDS.

Vasculitis: is an inflammation of blood vessels. It is not a disease but rather a disease process that occurs in a number of autoimmune connective tissue diseases, such as RA and lupus. No cause is known but in some cases hepatitis viruses are involved. Cells of the immune system, which cause inflammation, surround and infiltrate the affected blood vessels, destroying them and possibly damaging the tissues they supply.

–Microscopic polyangiitis: is a systemic pauci-immune necrotizing vasculitis that affects mainly small vessels. Pathogenesis is unkown.

Mechanism of Inflammation: 

Inflammation involves (but is not limited to) the generation of a chemokine gradient produced by various cells in response to inflammatory stimuli. Migrating leukocytes respond to this gradient and are directed to the site of tissue distress. This migration is controlled by a series of adhesive events occuring between the circulating leukocyte and the endothelial cell. Adhesion molecules expressed by both cell types as as molecular addresses, allowing the appropriate cell type into the site of tissue distress.

Persistent inflammation is a central feature of many diseases and invariably involves the cruitment and activaiton of inflammatory cells that lead to structural changes in the affected organs. In diseases of the lung, for example, over 100 inflammatory mediators have been implicated, and the blocking of a single mediator is unlikely to be effective. In fact, antoagonists for these molecules have so far proved less effective than drugs with a broad spectrum of anti-inflammatory effects, such as glucocorticoids (Dip, Vet. J. 179, 2009, 38-49, p. 39 1st ¶).

Adenosine: is an endogenous nucleoside consisting of the purine base adenine in glycosidic linkage with the sugar ribose. It is present at low concentrations in the extracellular space but is greatly increased under stressful conditions as the result of enzymatic cleavage of the nucleotide adenosine 5′-monophosphate (AMP) by the 5′-nucleotidase. Intracellular concnetrations of adenosine are kept low principally by its conversion to AMP by adenosine kinase, but it may also be degraded to inosine by adenosine deaminase (Dip, Id, p. 38).

Complement system: Studies implicate an important role for natural antibody and the classical pathway of complement in the inflammatory response. For example, ischemia-reperfusion injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. For example, US Pat Nos: 7,442,783 and 7,442,783 described conserved reion with type II NMHC proteins (corresponding to amino acids 592-603 of Mouse NMHC-IIB (the “N2 self-peptide) as representing a major epitope for bidning of natural IgM following ischmia in an intestinal model.  Carroll,  (US 8,324,352 and 13/668515) described isolated antibodies that bind the N2 self peptide and inhibit such inflammation. 

Treatment Strategies:

Corticosteroids (cortisone-like medicine or steroid):

–Methylprednisolone provides relief for inflamed areas of the body. It is used to treat a number of different conditions, such as inflammation (swelling), severe allergies, adrenal problems, arthritis, blood or bone marrow problems, eye or vision problems, lung or breathing problems (eg, asthma), lupus, skin conditions, kidney problems, ulcerative colitis, and flare-ups of multiple sclerosis. Methylprednisolone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions.

Methylprednisolone, a corticosteroid, is similar to a natural hormone produced by your adrenal glands. It is often used to replace this chemical when your body does not make enough of it. It relieves inflammation (swelling, heat, redness, and pain) and is used to treat certain forms of arthritis; skin, blood, kidney, eye, thyroid, and intestinal disorders (e.g., colitis); severe allergies; and asthma. Methylprednisolone is also used to treat certain types of cancer. 

Methylprednisolone is a systemic synthetic corticosteroid that exerts a wide range of physiologic effects similar to naturally occurring glucocorticoids. See Correa, Methylprednisolone