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The Studies On Mechanism Of Allergic Reaction To Penecillins

Posted on:2003-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:X TianFull Text:PDF
GTID:2144360065955998Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
To investigate the mechanism of allergic reaction to penecillins , the following studies have been done.1. The proliferation of T cell lines to different antigens To clarify the specific T cell response to haptens like penicillin G, we stimulated peripheral blood mononuclear cells(PBMCs) from penicillins-allergic patients with penecillin G (PG), phenylacetic acid(PHA), phenoxomethylpenicillin(PV), phenoxacetic acid(PHOA), ampicillin(AMP), N-phenylglycine (NPG), amoxicillin(AX), N- ( P-hydroxyphenyl) glycine(PHPG), 6-aminopenicillanic acid(6-APA). The positive ratios of T cell lines to PG, PHA, PV, PHOA, AMP,NPG, AX,PHPG, 6-APAwere 68.75%, 50%, 56.25%, 37.5%,50%, 37.5%, 37.5%, 31.25%, 43.75%, respectively.According to the specitivity to antigens, TCLs coule be divided into two groups: group A showed a broad reactivity, as the-5-TCLs restimulated by antigens, such as PG, AX and PHA; group B with a specitivity , as the TCLs proliferated only to one antigen.2.cytokines and allergyTo investigate the realationship between cytokines and penicillins allergy, we determined IL-4,IL-5 and IFN- Y levels in serum of 47 allergic patients by enzyme linked immunosorbent assay (ELISA).The allergic patients were divieded into two groups according to their histories:group A, of 36 patients with immediate hypersensation reactions(IHR), group B, of 11 patients with delayed hypersensation reactions (DHR);group C, of 10 normal controls with no allergy or negative skin test. The IL-4, IL-5 and IFN- Y levels of three groups were 0.17±0.15, 0.29±0.12 and 0.07±0.02; 0.10±0.10, 0.09±0.04 and 0.05±0.02; 0.19±0.14, 0.34±0.18 and 0.11±0.05, respectively. One way ANOVA showed that IFIR was associated with IL-4, and DFIR was associated with IL-4 and IFN- Y levels in serum, respectively. There was no associations between allergic and IL-5 levels in serum.3.IL-4, IFN- Y mRNA induction in T lymphocytes specific for penecillins in hypersensitivity reactionTo investigate the involvement of type l(Thl or Tel) and type 2-like(Th2 or Tc2) difference in penecillins allergy, we studied the expression of IL-4, IFN- Y mRNA in patients-derived peripheral blood lymphocytes following specific stimulation in vitro byreverse transcription and polymerase chain reaction (RT-PCR). The study involved 14 patients who developed immediate or delayed clinical manifestations of hypersensitivity to penecillins. PBMCs were stimulated with PG .Specific induction of IL-4 mRNA expression was observed in 4 of 7 patients with IHR, 1 of 7 patients with DHR, and 1 of 11 control subjects. IFN- y mRNA expression was oberserved in 6 of 7 patients with IHR, 2 of 7 patients with DHR, and 1 of 11 control subjects. The results indicated that IHR and DHR were associated with a mix response of type-1 and type-2 when PBMCs were specifically stimulated in invro:one patient with DHR showed a IL-4 response, and two patients with IHR showed a IFN- Y 's.4.The correlations between cytokines and antibodies Specific IgE, IgG and total IgE antibodys in serum of 34 allergic patients were detected by radioallergo- sorbent test(RAST) and ELISA..To patients with allergic histories and the patients with negetive IgE antibodies, the serum levels of IL-4 and IFN- Y had correlations to specific IgE; and the levels of IL-4, IL-5 and IFN-Y had correlations to specific IgG and total IgE. To the patients with negetive IgE antibodies the IL-4, IL-5 and IFN- Y serum levels had significant correlations to Specific IgE,IgG and total IgE.Conclusion: The results show that penicillins ,their side chains, and 6-APA could stimulated the proliferation of T cell lines. T cell lines generated by antigens can be divided into two types: cross-reactivitity and specifity. IHR was associated with IL-4, and DHR was associated with IL-4 and IFN- y levels in serum, respectively. IHR and DHR were associated with a mix response of type-1 and type-2 when PBMCs from penecillins allergic patients were specifically stimulated in vitro. The serum levels of I...
Keywords/Search Tags:penecillins, allergy, T cell line, cytokine, RT-PCR, ELISA, IgE, IgG, RAST
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