Hypersensitivity, mediators

Tajima S, Nishimura N, Ito K. 1985. Suppression of delayed-type hypersensitivity mediated by macrophage-like cells in mice with experimental liver injury. Immunology 54 57-64. 

Neumann S, Doubell TP, Leslie T, Woolf CJ (1996) Inflammatory pain hypersensitivity mediated by phenotypic switch in myehnated primary sensory neurons. Nature 384 360-364... 

Fong TA, Mosmann TR (1989) The role of IFN-gamma in delayed-type hypersensitivity mediated by Thl clones. J Immunol 143 2887-2893... 

In mice orally administered 0.5 or 5 mg/kg of an aqueous extract of chap u de couro daily for 7 days, immunosuppressive activity was observed, including inhibition of B cell antibody production and delayed-type hypersensitivity mediated by T cells, reducing subcutaneous tissue leukocyte infiltration (Pinto et al. 2007). 

Asthma is an extremely complex condition characterized by variable and reversible airways obstmction combiaed with nonspecific bronchial hypersensitivity (1 3). The cause of asthma, which is not always readily diagnosed (4), remains unknown. Days, if not weeks, ate needed to document the spontaneous reversal of the airways obstmction ia some patients. Asthmatics experience both an immediate hypersensitivity response and a delayed late-phase reaction, each mediated by a different pathway. Chronic asthma has come to be viewed as an inflammatory disease (5). The late-phase reaction plays a key role ia iaduciag and maintaining the inflammatory state which ia turn is thought to iaduce the bronchial hyperresponsiveness (6). The airways obstmction results from both contraction of airways smooth muscle and excessive bronchial edema. Edema, a characteristic of inflammatory states, is accompanied, ia this case, by the formation of a viscous mucus which can completely block the small airways. 

In addition to the proteins discussed above, a large number of reactive chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneumonias have also been described. Isocyanates and acid anhydrides are industrial chemicals that cause occupational asthma. Acid anhydrides, such as phthalic anhydride, seem to cause mainly type I reactions, whereas the IgE-mediated mechanism explains only a part of the sensitizations to isocyanates. Several mechanisms have been suggested, but despite intensive research no models have been generally accepted. The situation is even more obscure for other sensitizing chemicals therefore, the term specific chemical hypersensitivity is often used for chemical allergies. This term should not be confused with multiple chemical sensitivity (MCS) syndrome, which is a controversial term referring to hypersusceptibility to very low levels of environmental chemicals. ... 

In type III or immunocomplex-mediated allergy, IgG antibodies form complexes with antigen. At low exposures, the body is able to remove diese complexes, but if there is a severe exposure, immunocomplexes release a variety of proinflammatory cytokines. The involvement of this mechanism is clearest in serum sickness. This mechanism is also considered to be most important in the development of extrinsic allergic alveolitis (hypersensitivity pneumonitis, especially... 

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

Type IV allergic reactions are cell-mediated hypersensitivity reactions which are characterized by the expansion of T lymphocytes specific for foreign substances exposed on cell surfaces. In type FVa allergic reactions, this results in the cell-mediated destruction of the cells, whereas in type FVb allergic reactions an... 

Non-immune hypersensitivity via direct mediator release or direct activation of plasma-protein systems... 

The evidence that immediate hypersensitivity reactions may indeed be caused by an IgE-mediated allergic mechanism is also mainly indirect. However, some data support the concept that a subgroup of reactions may be IgE-mediated ... 

Positive basophil activation tests were reported in patients with immediate RCM hypersensitivity reactions, which may be regarded as another indirect indication for an IgE-mediated allergy [35]. 

The most common clinical picture of non-immediate RCM reactions is a macu-lopapular exanthema, which resembles other drug-induced T-cell-mediated hypersensitivity reactions. The reported onset of skin eruptions 2-10 days after the first exposure to a RCM and 1-2 days after re-exposure to the same substance is typical for an allergic drug reaction with a sensitization phase. 

Trcka J. Schmidt C, Seitz CS, et al Anaphylaxis to iodinated contrast material nonallergic hypersensitivity or IgE-mediated allergy AJR Am J Roentgenol 2008 190 666-670. 48... 

Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F, Ebner H, Ebner C IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. J Allergy Chn Immunol 2003 111 882-888. 

Clinical manifestations show striking variations of intensity in different patients, ranging from mild hypersensitivity reactions to severe anaphylactic shock and death (table 3). However, IgE-mediated reactions are usually more severe than non-IgE-medi-ated reactions [9]. In addition, IgE-mediated reactions to NMBAs have been shown to be more severe than reactions to other substances like latex in some series [9]. 

Table 4. Substances responsible for IgE-mediated hypersensitivity reactions in France. Results from seven consecutive surveys [9] (% values)... 

The rate of non-lgE-mediated immediate hypersensitivity reactions usually varies between 20 and 50% [1-7, 9], They are assumed to result from direct non-specific mast cell and basophil activation, which causes direct histamine release [19], Histamine release is predominantly found with the use of the benzylisoquinoUnes d-tubocurarine, atracurium and mivacurium, and the aminosteroid rapacuronium. Severe bronchospasm related to rapacuronium administration has been reported in children and adults. It might be related to the higher affinity of rapacuronium for M2 versus M3 muscarinic receptors [20]. Rapacuronium has been withdrawn from the market in the USA. 

Hypnotics. Common hypnotics are thiopental, propofol, midazolam, etomidate, ketamine and inhaled anesthetics. The incidence of hypersensitivity reactions with thiopental is rare. Recently, thiopental was involved in less than 1% of allergic reactions in France [9]. Ever since Cremophor EL, used as a solvent for some non-barbiturate hypnotics, has been avoided, many previously reported hypersensitivity reactions have disappeared. In the last French surveys, reactions to propofol accounted for less than 2.5% of allergic reactions, and reactions to midazolam, etomidate or ketamine appear to be really rare [9]. Finally, no immune-mediated immediate hypersensitivity reaction involving isoflurane, desflurane or sevoflurane has been reported despite their wide use. 

SH, Gendeh BS IgE-mediated hypersensitivity reaction to lignocaine - a case report. Trop Biomed 30 2005 22 179-183. 

NMBAs Immune-Mediated Hypersensitivity Reactions Are Predominant... 

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