Hev b 6.01 and Hev b 5 induce pro-inflammatory cytokines and chemokines from peripheral blood mononuclear cells in latex allergy.
BACKGROUND
Hev b 6.01 (prohevein) and Hev b 5 [acidic natural rubber latex (NRL) protein] are major IgE-binding allergens in NRL allergy.


OBJECTIVE
To examine allergen-specific cytokine and chemokine responses in NRL-allergic patients.


METHODS
Fourteen NRL-allergic patients and 10 healthy controls participated in the study. Hev b 6.01 and Hev b 5 were purified under non-denaturating conditions by chromatographic methods. Specific IgE antibodies were measured by ELISA and proliferation of peripheral blood mononuclear cells (PBMC) by (3)H-thymidine incorporation assay. Allergen-specific induction of cytokine and chemokine mRNA in PBMC was measured by real-time PCR and protein levels by ELISA. Surface expression of chemokine receptors was analysed by flow cytometry.


RESULTS
Twelve (86%) NRL-allergic patients had positive skin prick test reactions and IgE antibodies against Hev b 6.01, but less than 30% responded to Hev b 5. Cell proliferation against Hev b 6.01, but not against Hev b 5, was significantly increased. Both allergens elicited significantly higher expression of pro-inflammatory and T-helper type 2 cytokines (TNF, IL-12p40, IL-13) and chemokines (CCL3, CCL4, CCL20) in the NRL-allergic patients than in controls. Interestingly, mRNA expression of the regulatory cytokine TGF-beta1 was reduced, whereas IL-10 expression was enhanced after allergen stimulations in patients with NRL allergy. Finally, the NRL-allergic patients showed increased CCR4 expression on CD3(+)CD8(-) T cells and decreased CXCR3 expression on CD3(+)CD8(+) T cells.


CONCLUSIONS
Allergen-specific induction of cytokines and chemokines in PBMC and chemokine receptor expression on circulating T cells may contribute to the pathogenesis of NRL allergy.
Lehto
M
M
Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland. maili.lehto@ttl.fi
Kotovuori
A
A
Palosuo
K
K
Varjonen
E
E
Lehtimäki
S
S
Kalkkinen
N
N
Palosuo
T
T
Reunala
T
T
Alenius
H
H
D000328:Adult; D000485:Allergens / Q000032:analysis / Q000276:immunology*; D052179:Antigens, Plant; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D016753:Interleukin-10 / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D020315:Latex Hypersensitivity / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010940:Plant Proteins / Q000032:analysis / Q000276:immunology*; D012882:Skin Tests; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018709:Statistics, Nonparametric; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; C097982:Hev b 6.01 protein, Hevea brasiliensis; D053762:Interleukin-12 Subunit p40; D018793:Interleukin-13; D010940:Plant Proteins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C101800:allergen Hev b 5; D016753:Interleukin-10; D007073:Immunoglobulin E