165 Adverse Effects of Danazol in the Prophylactic Treatment ofHereditary or Acquired C1-Inhibitor Deficiency

W. Kreuz, E. Aygoren-Pursun, I. Martinez-Saguer, E. Rusicke, T. Klinge-

biel; University Hospital Frankfurt, Frankfurt, GERMANY.

RATIONALE: C1-Inhibitor (C1-INH)- deficiency, hereditary (HAE) or

acquired (AAE), is characterized by recurrent angioedema. Patients with

frequent and/or severe manifestations of HAE/AAE can be considerably

impaired in daily life. Prophylactic treatment is therefore important for

many patients. The attenuated androgen danazol can be used for long-

term prophylaxis in HAE/AAE. However, many adverse effects are recog-

nized. We aimed at assessing the whole range of adverse effects during

danazol prophylaxis in our own patient group.

METHODS: A retrospective chart analysis was performed. The charts of

all patients that received treatment with danazol were analyzed concerning

danazol-related adverse effects.

RESULTS: 93 patients with danazol treatment were identified (81 - HAE

type 1; 4 - HAE type 2; 5 - AAE; 3 - no C1-INH deficiency). The duration of

danazol administration ranged from 0,1 to 25.0 years, administered doses

ranged from 0.14 mg/d to 1200 mg/d. Main adverse effects encountered

were of psychopathological nature, i.e. depression (47%), indisposition

(28%) and panic disorder (10%). Moreover headache (40%), considerable

weight gain (39%), arterial hypertension (30%) and migraine (10%) were

documented. Dose-dependency was seen in affected females who suffered

from virilisation (79%). Symptoms were frequently reversible with discon-

tinuation of the drug. Only 10% of patients experienced no adverse affects

at all, whereas the majority of patients suffered from multiple adverse ef-

fects simultaneously.

CONCLUSIONS: The administration of the attenuated androgen danazol

is limited by a large array of adverse effects, which is particularly dissat-

isfying in view of the long-term nature of the treatment.

166 T-Cell Receptor (TCR)-Mediated Upregulation of BLT1 (LTB4Receptor) Expression and Activation of Human T Cells byLTB4

A. Ahuja, A. Dakhama, H. Ohnishi, J. J. Lucas, E. W. Gelfand; National

Jewish Medical and Research Center, Denver, CO.

RATIONALE: BLT1, the high affinity receptor for leukotriene B4 (LTB4),

has been implicated in the development of airway hyperresponsiveness and

allergic airway inflammation in murine models and in asthma (JACI

117:577-582, 2006). This study investigated the induction of BLT1 expres-

sion and activation of human peripheral blood T cells via LTB4-BLT

interactions.

METHODS: T cells were isolated to high purity (>97% CD31) by neg-

ative selection from peripheral blood of healthy human subjects. Cells were

stimulated in culture with anti-CD3/anti-CD28, followed by analysis of

BLT1 expression on CD41 or CD81 T cells. Activation of T cells follow-

ing ligation of BLT1 by LTB4 was assessed by intracellular Ca21 mobili-

zation and mitogen-activated protein kinase (MAPK) phsophorylation.

RESULTS: BLT1 expression was not detected on freshly isolated, resting

(non-stimulated) CD4 or CD8 T cells. Following activation of cells with

anti-CD3/anti-CD28, BLT1 expression was induced in a time-dependent

fashion on both CD4 and CD8 T cells. Addition of LTB4 triggered intracel-

lular Ca21 mobilization and MAPK phosphorylation in activated but not in

resting CD4 and CD8 T cells.

CONCLUSIONS: Both CD4 and CD8 T cells express BLT1 upon TCR

activation. Engagement of BLT1 with LTB4 results in activation of these

cells. Together, with observations made in mice, these findings suggest

an important role for the LTB4-BLT1.

Funding: This work was supported by NIH grants HL-36577 and HL-

61005, and by EPA grant R825702

J ALLERGY CLIN IMMUNOL

VOLUME 119, NUMBER 1

Abstracts S43

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167 The Role Of Th1 And Th2 Response In Allergic Rhinitis

Children With Or Without Sensitization To Food AllergensA. Nakonechna1, T. Umanetz2, V. Lapshin2, A. R. D. van Bergen3;1National Medical University, Kiev, UKRAINE, 2Institute of Pediatry,

Obstetrics and Gynaecology, Kiev, UKRAINE, 3Novidec Ltd, Neston,

UNITED KINGDOM.

RATIONALE: Patients with allergic rhinitis (AR) show allergic symp-

toms to fruits, vegetables and nuts in 48-72%. Oral allergy syndrome

(OAS) is based on cross-reaction of pollen-allergen specific IgE with ho-

mologous food proteins. In AR pathogenesis there is a prevalence of Th2

response with an ensuing increase in cytokines production.

This study investigated the cytokines production by Th1 and Th2 in AR

children with or without sensitization to food allergens.

METHODS: Sixty children (8-12 years) with AR were observed. Group I

32 AR patients; group II 28 AR and OAS patients. Sensitivity to pollen

allergens was tested by SPT. Food allergy in OAS patients was determined

by questionnaire and SPT. IL-5, IL-10, g-IFN levels were measured

by ELISA.

RESULTS: 26.7% of patients were sensitized to grass’, 20.0% to trees and

53.3% to grass’, trees and weeds pollen. OAS patients more often had pos-

itive SPT to birch, alder, mugwort. 71.4% of gr.II had allergic reactions to

food: hazelnut, apple, carrot, peanut.

Fruits and vegetables sensitivity was confirmed by SPT in 78.6%. Blood

eosinophils and total IgE were elevated in all patients. IL-5 production

increased to 163.465.1 pg/ml in gr.I and 198.366.2 in gr.II, and IL-10 to

14669 in gr.I and 17768 in gr.II. The g-IFN level decreased to 257.666.2

in gr.I and 232.665.2 in gr.II.

CONCLUSIONS: AR children can be sensitized to food allergens that

may cause OAS, especially in patients with increased functional activity

of Th2. The function of Th2 (identified by cytokines production) was acti-

vated in AR patients, especially in combination with OAS.

Funding: National Medical University

168 CD41CD251 Cells and Laboratory Animal AllergyH. Jeal, A. Newman Taylor, M. Jones; NHLI @ Imperial

College, London, UNITED KINGDOM.

RATIONALE: The functionality of T regulatory cells has been shown to

be diminished in non-atopic individuals compared with atopics. In this

pilot study we investigated whether a difference in the ability of

CD41CD251 T cells to suppress proliferation and cytokine production

could be seen between individuals with and without laboratory animal

allergy, a common occupational health problem.

METHODS: CD41CD251 and CD41CD25- T cells were isolated from

the peripheral blood of 12 currently exposed rat skin prick test (SPT) pos-

itive and 10 rat SPT negative individuals and 2 non-exposed controls using

MACs immunomagnetic beads. Inhibition of proliferation and cytokine

production was analysed.

RESULTS: CD41CD25- cells proliferated to a significantly greater de-

gree than PBMCs (p<0.01) and CD251 cells (p<0.001) in all individuals.

Inhibition of proliferation to rat by CD41CD251 T cells did not differ be-

tween cases and exposed controls but was much higher in non exposed con-

trols. IL-5 suppression was greater in exposed controls (>50% suppression

5 4/6) compared with cases (>50% suppression 5 1/7).

CONCLUSIONS: Differences in the ability of CD41CD251 cells to

suppress proliferation could not be seen between cases and exposed con-

trols. However failure of these cells to suppress IL-5 production in cases

could contribute to the development of their allergic disease.

Funding: Clinical Research Committee at the Royal Brompton Hospital