Cytokine mRNA expression in patients with mild allergic asthma following low dose or cumulative dose allergen provocation.
BACKGROUND
Allergen provocation is a very useful way to study the inflammatory response in asthmatic patients. Although cumulative dose regimens are most often applied, another provocation model with repeated inhalations of low doses of allergens has recently come into use.


OBJECTIVE
We were interested to compare these two allergen provocation models. To evaluate the inflammation induced by either model, we examined the mRNA expression of several cytokines that are implicated in the orchestration of the inflammatory response observed in asthma.


METHODS
Interleukin (IL)-4, IL-5, IL-13 and interferon (IFN)-gamma mRNA expression was analysed in bronchoalveolar lavage (BAL) cells and peripheral blood (PB) CD4+ and PB CD8+ T cells following any of the two provocation regimens. IL-4 and IFN-gamma mRNA expression was analysed by a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) method, while IL-5 and IL-13 were analysed semiquantitatively, before and after allergen provocation with either model.


RESULTS
After low dose provocations none of the cell populations studied showed a clear change in the pattern of IL-4 or IFN-gamma gene expression. In contrast, after cumulative dose provocation there was a clear tendency towards an increased IL-4 mRNA expression in BAL cells, correlating with a significant increase in IL-4 mRNA in PB CD4+ as well as in CD8+ T cells (P = 0.005 and P = 0.04, respectively). Regardless of the allergen provocation method used, in PB IL-4 mRNA was preferentially expressed by CD4+ cells while IFN-gamma was expressed more by CD8+ cells. IL-5 transcripts increased after low dose provocations in PB CD4+ T cells in six of eight patients, while after cumulative dose provocation IL-5 mRNA increased in BAL cells in six out of nine patients but decreased especially in PB CD8+ T cells in six out of eleven patients, suggesting an accumulation of IL-5 expressing cells to the lungs.


CONCLUSIONS
Thus, the cumulative dose provocation regimen can induce a more pronounced Th2-like immune response in asthmatic patients than the low dose provocation model.
Prieto
J
J
Department of Medicine, Division of Respiratory Medicine, St. Erik's Eye Hospital, Karolinska Institute, S-171 76 Stockholm, Sweden.
Van Der Ploeg
I
I
Roquet
A
A
Gigliotti
D
D
Dahlén
B
B
Eklund
A
A
Grunewald
J
J
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D001249:Asthma / Q000235:genetics* / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
D000485:Allergens; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma