Anti-inflammation actions

The wide range of inflammation-related factors that adipocytes secrete is linked to the inflammatory response that the tissue exhibits in obesity [1]. Obesity in general, like an increasing number of other diseases, is characterised by a state of mild chronic inflammation, and adipose tissue plays a central role in this. The production of most inflammation-related adipokines increases markedly in obesity and there is an elevated circulating level of a number of these factors as well as of other inflammatory markers such as C-reactive protein (CRP). The increased production of inflammatory adipokines (and decreased production of adiponectin with its anti-inflammatory action) in the obese is considered to play a critical role in the development of the obesity-associated pathologies, particularly type 2 diabetes and the metabolic syndrome [1]. 

Another drug that has been found to have anticytokine activity is pentoxifylline. It was initially characterized as a haemorheologic agent for the treatment of peripheral vascular diseases [141]. In addition, it was also found to be capable of inhibiting the pro-inflammatory actions of IL-1 and TNEa on neutrophil function and cytokine production by monocytic cells [142]. Its mechanism of action is the inhibition of phosphodiesterases, leading to increased intracellular levels of cyclic adenosine monophosphate [143]. Besides its effects on the cytokine network, pentoxifylline also exerted an anti-fibrogenic action in cultures of fibroblasts and in animal models of fibrosis [144] and could therefore be an attractive candidate for targeting hepatic inflammation. 

Finally there has been a growing interest in the development of selective leukotriene inhibitors. Bay Y 1015 (R-(-)-2-cycloheptyl-N-methylsulfonyl-(4-(2-quinolinyl-methoxy) phenyl)-acetamide) is a quinoline-type 5-lipoxygenase-activating protein inhibitor which was effective in inhibiting inflammation in a dextran sulfate model of mouse colitis [112]. Whether these compounds can also exert their anti-inflammatory action through inhibition of endothelial cell activation needs to be established. 

Tobramycin Dexamethasone Ophthalmic (TobraDex) [Antibiotic/Anti-inflammatory] Uses Ocular bacterial Infxns associated w/ significant inflammation Action Antibiotic w/ anti-inflammatory Dose Oint soln Caution [C, M] Contra Aminoglycoside sensitivity Disp Oint susp 2.5, 5, 10 mL tobramycin 0.3% dexamethasone 0.1% SE Local irrita-tion/edema see Tobramycin EMS See Tobramycin OD Unlikely w/ ophthalmic form... 

Comfrey (Symphytum officinale) Uses Topical treatment of wounds, bruises, sprains, inflammation Action Multiple chemical components, allantoin promotes cell division, rosmarinic acid has anti-inflammatory effects, tannin possesses astringent effects, mucilage is a demulcent w/ anti-inflammatory properties, pyrrolizidine alkaloids cause hepatotox Available forms Topical application w/ 5—20% of herb applied on intact skin for up to 10 d Contra Do not take orally d/t hepatotox, do not use if PRG or w/ lactation Notes/SE N/V, exfoliative dermatitis w/ topical use Interactions T Risk of hepatotox W/ ingestion of borage, golden ragwort, hemp, Petasites EMS None... 

Fauveau and Le Paire 23 studied the anti-flash effect of potassium chloride and of other salts and concluded that the lowering of the temperature of the gas which undoubtedly results from their volatilization and dissociation is insufficient to account for the extinction of the flash. Prettre24 found that the chlorides of sodium and of lithium, and other alkali metal salts which are volatile, had the same effect as potassium chloride. He found that small amounts of potassium chloride, volatilized in mixtures of carbon monoxide and air, had a powerful anti-oxidant action and a correspondingly large effect in raising the temperature of inflammation of the gas. Some of his results are shown in the table below. He found that potassium chloride was without effect... 

The role of A3 adenosine receptors in modulating inflammatory responses was also confirmed in mice after its targeted deletion. Adenosine mediates an increase in cutaneous vascular permeability leading to extravasation of serum proteins as an important mechanism in the development of an inflammatory response. It turned out that this reaction is dependent on the presence of A3 adenosine receptors on mast cells as both A3 knockout mice and mice lacking mast cells showed no response (Tilley et al. 2000). Adenosine accomplishes mainly an anti-inflammatory effect which is generally assumed to be mediated by the A2A subtype (Sitkovsky et al. 2004). However, A3 agonists were also found to produce anti-inflammatory actions, for example by inhibiting neutrophil function. Such a contribution to inhibition of inflammation was recently confirmed in a comparison of A2A and A3 knockout mice (van der Hoeven et al. 2008). 

Mechanisms for the Pro and Anti-inflammatory Actions of Adenosine A Receptor During Airway Inflammation... 

Whatever the mechanism of action for the inhibition of 5-lipoxygenase by flavonoids, it appears to be distinct from the antioxidant properties of these compounds. The results comparing antioxidant activity with leukotriene inhibitory activity clearly demonstrate this distinction. The profound effects of metabolic transformation on the anti-inflammation activity of dietary flavonoids such as quercetin must also be considered in relation to in vitro studies, and further highlights the need to use actual metabolic forms of flavonoids rather than the free aglycone or glycosides occurring in the diet. 

The anti-inflaminatory action of bromelain preparations is the result of dif-fjrjnt mechanisms thatnft simultaneous 11. First there is, as described sbevr, the depletion of the plasma kallikrein system, inhibiting the generation of bndykinin, a known chemical mediator of inflammation. Second, there is a negative action... 

Anti-inflammatory action. Chronic or recurrent inflammation probably has a role in many types of human cancer. 

The separation of nonsteroidal anti-inflammatory drugs (NSAIDs) has recently attracted considerable interest. Nonsteroidal anti-inflammatory drugs are agents that, in addition to having anti-inflammatory action, also have analgesic, antipyretic, and platelet-inhibitory properties. They are used primarily in the treatment of chronic arthritic conditions and certain soft tissue disorders associated with pain and inflammation. 

In the presence of aspirin, AA, EPA, and DHA are converted to form epi-lipoxins, lipoxins, and resolvins that, in turn, enhance the formation of eNO (3, 4, 96). Lipoxins possess potent anti-inflammatory actions (reviewed in References 3 and 4). In addition, NO not only blocks the interaction between leukocytes and the vascular endothelium during inflammation but also stimulates the formation of PGI2, a potent vasodilator and platelet anti-aggregator, from AA (97, 98). 

Fish is the most important source of the n-3-PUFAs Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and populations consuming fish have lower heart rates. Other important parameters reported were lower blood pressure and higher HDL cholesterol. The strongest evidence for an effect of n-3-fatty acids on disease is the inverse relationship between diet, blood, and tissue levels and coronary heart disease. n-3-PUFAs prevent heart disease by preventing arrhythmias, generating prostanoids and leukotrienes with anti-inflammatory actions, and inhibiting synthesis of cytokines and mitogens that provoke inflammation and promote plaque formation. ... 

While aspirin significantly inhibits peripheral prostaglandin and thromboxane synthesis, paracetamol is less potent as a synthetase inhibitor than the NSAIDs, except in the brain, and paracetamol has only a weak anti-inflammatory action. It is simple to ascribe the analgesic activity of aspirin to its capacity to inhibit prostaglandin synthesis, with a consequent reduction in inflammatory edema and vasodilatation, since aspirin is most effective in the pain associated with inflammation or injury. However, such a peripheral effect cannot account for the analgesic activity of paracetamol, which is less well understood. 

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