Regulation of Inflammatory Response

Pycnogenol reduces the production of interleukin-6 and restores the activity of natural killer cells in retrovirus-infected animals. Pycnogenol delays the development of immune dysfunctions secondary to retrovirus infection by restoring the imbalanced cytokine secretion by T helper 1 and T helper 2 cells. 

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Not more than 20 years ago, a limited number of laboratories around the world were attempting to investigate a small peptide mediator that seemed to have neutrophil chemotactic properties and was thought to be involved in regulation of inflammatory responses. This molecule was identified and... 

Furnkranz A. and Leitinger N. (2004). Regulation of inflammatory responses by oxidized phospholipids structure-function relationships. Curr. Pharmaceut. Design 10 915-921. 

Fig. 11. Airway epithelial cells as sources of cytokines and chemokines in the airways. Airway epithelial cells express and release a variety of cytokines/chemokines, adhesion molecules, and lipid mediators, and thereby participate in the regulation of inflammatory responses in the airways.

Complement. Complement is an extensive series of glycoproteins and protein inhibitors whose function includes major cytolytic effects, mediation of opsonization, and modulation of inflammatory responses. Activation of this system plays an important role in host defense leading to destruction of microorganisms. It also results in generation of anaphylotoxins which induce mediator release and "split products" that mediate membrane damage, either directly through structural alteration or indirectly, via cell chemotaxis and regulation. 

Cytokines and antagonists (2—4), intercellular proteins produced by immune cells, play an important role in the regulation of immune responses. Cytokines are present in a variety of tissues under normal conditions. Through insufficient or excessive production, these macromolecules can mediate chronic inflammatory diseases. An inability to respond to cytokines, eg, interleukin 1 (IL-1) or interleukin 2 (IL-2), may lead to an immunosuppressive state, whereas over-production can result in severe shock, autoimmune disease, or immunopathological conditions, such as leukemia and rheumatoid arthritis (RA). Specific communications between immune cells are constantly modulated by naturally occurring inhibitors. 

The cytokine IL-lp serves a cenhal role in the initiation and coordination of inflammatory responses, both in the periphery and in the CNS. Neurons, ashocytes, microglia, and epithelial cells in the brain constitutively express this cytokine, and its central effects in regulating cenhal inflammatory responses... 

The molecular mechanism of the NO pro-inflammatory activity is also multifaceted NO regulates the inflammatory responses by cell-specific inhibition of the transcription factor NF-kB, IL-ip, interferon-y (IFNy). At sites of inflammation, increased free radical activity is associated with the activation of the neutrophil NADPH-oxidase and/or the uncoupling of a variety of redox systems, leading to a substantial increase in ROS. Free radicals thus produced, have the capacity to mediate tissue destruction, either alone or in concert with proteases [53]. 

Gonzalez-Rey E, Femandez-Martin A, Chorny A, Martin J, Pozo D, Ganea D, Delgado M (2006) Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis Down-regulation of inflammatory and autoimmune responses. Am J Pathol 168 1179-1188. 

Ramaiah SK, Rittling S (2007) Role of osteo-pontin in regulating hepatic inflammatory responses and toxic liver injury. Expert Opin Drug Metab Toxicol 3(4) 519-526. doi 10.1517/17425225.3.4.519... 

The primary functions of lymphocytes are to control and be the effector cells for the immune system. Many of these cells also are important synthetic sites for various cytokines. Lymphocytes can be functionally divided into cells that display cell-mediated immunity (T cells) and those that are responsible for humoral immunity (B cells Table 98-2). Several different T-cell subtypes are found in peripheral blood. These include the cytotoxic suppressor T cells (CDS), which attack intracellular pathogens and regulate the size and duration of the immune response, as well as helper T cells (CD4). The latter cells are responsible for delayed hypersensitivity, stimulation of B-ceU differentiation (maturation), and antibody production, in addition to regulation of inflammatory reactions. B lymphocytes ultimately become plasma cells, which produce immunoglobulin specific for an antigen attached to the cell s surface. 

E. M. Sternberg, The stress response and the regulation of inflammatory disease, Annals of Internal Medicine, 117, 1992, 854-66. 

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