Get access

Peripheral blood T lymphocytes from asthmatic patients are primed for enhanced expression of interleukin (IL)-4 and IL-5 mRNA: associations with lung function and serum IgE

Authors


Postma Division of Pulmonology, Department of Internal Medicine, University Hospital Groningen, PO Box 30001, 9700 RB, Groningen, The Netherlands.

Abstract

Background

The TH2-like cytokines interleukin (IL)-4 and IL-5 play a pivotal role in airway wall inflammation in asthma and these cytokines are increased in peripheral blood and bronchoalveolar lavage fluid from asthmatic patients. It is unclear why specifically TH2-like cytokines are increased in asthmatic patients. A possible explanation may be an impaired adenylyl cyclase activity, which has been observed in peripheral blood mononuclear cells of asthmatics.

Objective

To assess interferon (IFN)-γ, IL-4 and IL-5 mRNA expressions and their control by prostaglandin E2 (PGE2), which activates adenylyl cyclases, of peripheral T lymphocytes from patients with moderately severe asthma and healthy controls.

Methods

Peripheral blood T lymphocytes from asthmatics and healthy controls were isolated and stimulated with antibodies against CD3 plus CD28 in the absence and presence of increasing concentrations of PGE2. IFN-γ, IL-4 and IL-5 mRNA levels were detected by reverse transcription-polymerase chain reaction.

Results

In contrast to IFN-γ mRNA, IL-4 (P = 0.03, n = 8) and IL-5 (P < 0.05, n = 5) mRNAs in the asthma group were significantly higher than in controls (n = 4). In addition, IL-5 showed a significant inverse correlation with forced expiratory volume (FEV1) (P < 0.04, n = 5), whereas IL-4 positively correlated with PC20adenosine-monophosphate (AMP) (P < 0.02, n = 8). Accumulation of mRNA for IFN-γ, IL-4 and IL-5 mRNA were significantly diminished by 10−5 m PGE2 in both asthmatics and controls. In contrast, 10−6 m PGE2 significantly down-regulated IFN-γ and IL-4 mRNAs (P < 0.05 for both IFN-γ and IL-4, n = 4) in the control group, whereas this was not observed for IL-4 mRNA in the asthma group (n = 7).

Conclusions

Activated peripheral blood T lymphocytes from asthma patients display higher levels of IL-4 and IL-5 mRNA in vitro, which may be due to a diminished activity of adenylyl cyclase. A new observation is that higher IL-4 mRNA levels are associated with less severe AMP responsiveness, which might be due to a negative feedback loop of IL-4 production by mast cells.

Ancillary