Inflammatory reaction mediators

Jatrorrhizine was found to possess anti-inflammatory activity as measured in the cobra venom factor-induced (CVF) rat paw edema. CVF edema was used to examine jatrorrhizine and other substances in order to detect novel compounds, since it has been shown that joint cyclooxygenase and lipoxygenase inhibitors, as well as immunoreactive drugs, exhibit more pronounced inhibitory effects on CVF in comparison to carrageenin-induced edema. CVF edema is dependent on activation of the complement system which plays an important role in acute and chronic inflammatory reactions, mediating the activity of immune complexes. This test system represents a functionally new type of acute inflammation via activation of the alternative complement pathway [290]. 

Figure 23.18 Action of glucocorticoids (GCs) in suppressing immune and inflammatory reactions mediated by cytokines. 

Allergic Seasonal or Perennial Rhinoconjunctivitis. Histamine can cause all pathologic features of allergic rhinitis (35—37), with the exception of late-phase inflammatory reactions. Pmritus is caused by stimulation of receptors on sensory nerve endings prostaglandins (qv) may also contribute. Sneering, like pmritus, is an H -mediated neural reflex and can also be mediated by eicosanoids. Mucosal edema, which manifests as nasal... 

Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, increased vascular permeability, complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling. 

Immunoenhancement, which, as adverse effect, may lead to immune-mediated diseases such as hypersensitivity reactions and autoimmune diseases. Hypersensitivity reactions are the result of normally beneficial immune responses acting inappropriately, causing inflammatory reactions and tissue damage. The two most frequent manifestation of chemical-induced allergy are contact hypersensitivity and respiratory sensitization, both of which can have a serious impact on quality of life and represent a common occupational health problem. Hypersensitivity reactions are often considered to be increased at such a rate to become a major health problem in relation to environmental chemical exposure. 

After damage or infection, monocytes and KCs in the area detect the damaged cells or infectious agent and respond with release of primary mediators such as TNFa, IL-1 and some IL-6. These cytokines activate the surrounding cells, that respond with a secondary, amplified release of cytokines. This second wave includes large amounts of IL-6, which induce the synthesis of acute phase proteins in hepatocytes and chemoattractants such as IL-8 and MCP-1. These events will then lead to the typical inflammatory reactions. Both IL-1 and TNFa activate the central regulatory protein of many reactions involved in immunity and inflammation, nuclear factor kappa B (NFkB). These cytokines cause dissociation of NFkB from its inhibitor IkB, which makes translocation of NFkB to the nucleus possible. In the nucleus active NFkB induces the transcription of the second wave cytokines (see also Chapter 7 for the molecular mechanisms of cytokine-mediated cell activation). 

These reactions are mediated by production of sensitized T-lymphocytes. On contact with antigen, an inflammatory reaction is generated which includes contact dermatitis, fever and photosensitization. 

Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between the effects of intravenously administered histamine and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic (such as urticaria) and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion (see Chapter 62) and functions as a neurotransmitter and neuromodulator (see Chapters 6 and 21). Newer evidence indicates that histamine also plays a role in chemotaxis of white blood cells. 

Although the cellular and molecular mechanisms underlying fibrosis are not fully explained, it is assumed that an inflammatory reaction is the initiating factor in the early stage of fibrosis and that this inflammatory process continues during the fibrotic process [77, 105, 106], Kupffer and endothelial cells are considered to be the most important resident cells involved in the local production of inflammatory mediators [24, 28, 29, 76], Besides causing the activation of HSC, the inflammatory mediators induce the expression of adhesion molecules, such as ICAM-1 and VCAM on endothelial cells, that direct neutrophils and monocytes into the inflamed liver tissue [41-43], Expression of adhesion molecules is also shown for KC and stellate cells [42, 107], Furthermore, chemotactic compounds are released by endothelial and KC to attract immune competent cells... 

Histamine A mediator of inflammatory reactions in the body, which may be part of an allergic reaction. Present in preformed granules in mast cells and basophils. 

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