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.

Abstract

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. To assess interferon (IFN)-gamma, 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. 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-gamma, IL-4 and IL-5 mRNA levels were detected by reverse transcription-polymerase chain reaction. In contrast to IFN-gamma 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-gamma, 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-gamma and IL-4 mRNAs (P < 0.05 for both IFN-gamma and IL-4, n = 4) in the control group, whereas this was not observed for IL-4 mRNA in the asthma group (n = 7). 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.