PURPOSE: Patients with a history of allergic reaction to penicillin, but with no detectable specific IgE, are common and pose a dilemma. Challenge tests are considered to be the diagnostic gold standard. The aim of this study was to identify subgroups of patients with very low risk for reactions who could be safely tested using a more rapid and simple procedure. METHODS: A total of 580 consecutively referred adult patients with a history of non-serious cutaneous allergic reactions to penicillin, but with no IgE, were challenged with therapeutic doses of penicillin V (phenoxymethylpenicillin), penicillin G (benzylpenicillin), or both. RESULTS: Only 14 of 580 patients had a positive challenge test. In 11 of the 14, a reaction to challenge occurred within 2 hours, and none were anaphylactic. The year of the original reaction was known for 555 patients; a positive challenge was seen in only 0.4% of those with an original reaction >15 years before challenge, but in 4.6% of those with a more recent original reaction (P=0.001). Onset of a reaction within the first day of the original exposure was a predictive factor for a positive challenge (P=0.001) in patients challenged within 15 years of the original reaction. CONCLUSIONS: Among suspected penicillin-allergic patients with non-severe skin reactions and no detectable specific IgE, the subgroup of patients who originally reacted more than 15 years previously had very low risk for reacting to a challenge. The risk was higher in patients with a more recent original reaction, especially if the symptoms had occurred within the first day of exposure.
Adult ; Drug Hypersensitivity ; Exanthema ; Humans ; Hypersensitivity ; Immunoglobulin E ; Penicillin G ; Penicillin V ; Penicillins ; Risk Factors ; Skin

The present study was undertaken to investigate the effect of acute administration of ethanol on production of cytokines such as IL-1j3, IL-2, IL-6, IL-10 and TNF-a, induction of penicillin V-induced active fatal anaphylaxis, and resistence to Salmonel/a typhimurium infection in mice. Ethanol administration into mice was performed by intraperitoneal injection of 0.5 ml of 20 % ethanol for 3 consecutive days before induction of cytokines with lipopolysaccharide (LPS), Con A or Salmone/la injection. Serum levels of cytokines were measured by ELISA. It was found that ethanol administration significantly inhibited both the serum levels of all cytokines examined and the resistance of mice to S. typhimurium. However, ethanol administration failed to prevent penicillin-induced fatal anaphylaxis. Taken together, the present results may need new insights in the diagnosis and treatment of various immunologically-mediated diseases.
Anaphylaxis* ; Animals ; Cytokines* ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Ethanol ; Injections, Intraperitoneal ; Interleukin-10 ; Interleukin-2 ; Interleukin-6 ; Interleukins ; Mice* ; Penicillin V* ; Penicillins* ; Salmonella Infections* ; Salmonella*

BACKGROUND: Anti-IgE mAb which binds circulating but not receptor-bound IgE has been shown to be effective in treatment for asthma and other allergic diseases. However, the mechanisms by which anti-IgE mAb influences the pathophysiological responses are remained to be illustrated. This study was undertaken to examine the therapeutic efficacy of non-anaphylactogenic anti-mouse IgE mAb using murine models of IgE-induced systemic fatal anaphylaxis. METHODS: Active systemic anaphylaxis was induced by either penicillin V (Pen V) or OVA and passive systemic anaphylaxis was induced by either anaphylactogenic anti-mouse IgE or a mixture of anti-chicken gamma globulin (CGG) IgG1 mAb and CGG. The binding of the Fc portion of anti-IgE to CHO-stable cell line expressing mouse FcgammaRIIb was examined using flow cytometry. Fc fragments of anti-IgE mAb were prepared using papain digestion. The expression of phosphatases in lungs were assessed by Western blotting and immunohistochemistry. RESULTS: Anti-IgE mAb prevented IgE- and IgG-induced active and passive systemic fatal reactions. In both types of anaphylaxis, anti-IgE mAb suppressed antigen-specific IgE responses, but not those of IgG. Anti-IgE mAb neither prevented anaphylaxis nor suppressed the IgE response in FcgammaRIIb-deficient mice. The Fc portion of anti-IgE mAb was bound to murine FcgammaRIIb gene-transfected CHO cells and inhibited systemic anaphylaxis. Anti-IgE mAb blocked the anaphylaxis-induced downregulation of FcgammaRIIb-associated phosphatases such as src homology 2 domain-containing inositol 5-phosphatase (SHIP) and phosphatase and tensin homologue deleted on chromosome ten (PTEN). CONCLUSION: Anti-IgE mAb prevented anaphylaxis by delivering nonspecific inhibitory signals through the inhibitory IgG receptor, FcgammaRIIb, rather than targeting IgE.
Anaphylaxis* ; Animals ; Asthma ; Blotting, Western ; Cell Line ; CHO Cells ; Cricetinae ; Digestion ; Down-Regulation ; Flow Cytometry ; gamma-Globulins ; Immunoglobulin E ; Immunoglobulin Fc Fragments ; Immunoglobulin G* ; Immunohistochemistry ; Inositol ; Lung ; Mice* ; Ovum ; Papain ; Penicillin V ; Phosphoric Monoester Hydrolases

Capsaicin, the pungent principle of hot peppers, is a neurotoxin that depletes unmyelinated primary sensory neurons (polymodal nociceptors) of neuropeptides like tachykinins. However, the role of capsaicin-sensitive sensory nerve in the production of cytokines, penicillin V (PEV)-induced active fatal anaphylaxis and other immune responses is not yet fully established. Neonatal mice were pretreated s.c. with a single injection of 10 ug of capsaicin per mouse in volume of 20 ul within 5 days of age. Using 5-8 week old mice pretreated as neonates with capsaicin, the capsaicin- pretreated and vehicle-treated control mice were examined for various parameters of immune responses described above. For the induction of active fatal anaphylaxis with PEV, 8 week old mice pretreated as neonates and age-matched capsaicin- untreated control mice were sensitized i.p. with 500 ug of PEV-ovalbumin conjugate plus 2*10(9) B. pertussis and 1.0 mg alum and challenged i.v. with PEV-bovine serum albumin conjugate 14 days later. It was found that neonatal capsaicin-pretreatment significantly enhanced contact hypersensitivity to TNCB and hemagglutination response to SRBC, but significantly inhibited the proliferation response of rnurine splenocyte to Con A and LPS. Interestingly, neonatal capsaicin pretreatment significantly inhibited the intensity of PEV-induced active fatal anaphylaxis and decreased the mortality due to anaphylactic shock. It also significantly inhibited LPS- induced production of cytokines such as TNF-a, IL-1B, IL-6, IL-10, and IL-12. The capsaicin-pretreatment also resulted in an inhibition of the activation of NF-kB. Taken together, these data showed for the first time that neonatal capsaicin-pretreatment significantly inhibited an antibiotic (PEV)-induced anaphylaxis and production of various cytokines, and suggest that capsaicin-sensitive primary sensory nerve may play an important regulatory role in active fatal anaphylaxis and cytokine production, thus potentially presenting tools for immune intervention. In particular, the data presented also indicated the possibility to selectively down-modulate cytokine production and NF-kB activation may offer a broad application for therapeutic intervention in neuroimmunological diseases and other pathological situations.
Anaphylaxis ; Animals ; Capsaicin* ; Cytokines ; Denervation* ; Dermatitis, Contact ; Hemagglutination ; Humans ; Infant, Newborn ; Interleukin-10 ; Interleukin-12 ; Interleukin-6 ; Mice ; Mortality ; Neuropeptides ; NF-kappa B ; Penicillin V ; Sensory Receptor Cells ; Serum Albumin ; Tachykinins ; Whooping Cough