Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma

Abstract

Allergen-reactive T helper type-2 (Th2) cells and proinflammatory cytokines have been suggested to play an important role in the induction and maintenance of the inflammatory cascade in allergic asthma. We compared the plasma concentrations of novel proinflammatory cytokines IL-17 and IL-18, other proinflammatory cytokines IL-6 and IL-12, Th2 cytokines IL-10 and IL-13, and intracellular interferon-gamma (IFN-gamma) and IL-4 in Th cells of 41 allergic asthmatics and 30 sex- and age-matched health control subjects. Plasma cytokines were measured by enzyme-linked immunosorbent assay. Intracellular cytokines were quantified by flow cytometry. Plasma IL-18, IL-12, IL-10, IL-13 concentrations were significantly higher in allergic asthmatic patients than normal control subjects (IL-18: median 228.35 versus 138.72 pg/ml, P < 0.001; IL-12: 0.00 versus 0.00 pg/ml, P = 0.001; IL-10: 2.51 versus 0.05 pg/ml, P < 0.034; IL-13: 119.38 versus 17.89 pg/ml, P < 0.001). Allergic asthmatic patients showed higher plasma IL-17 and IL-6 concentrations than normal controls (22.40 versus 11.86 pg/ml and 3.42 versus 0.61 pg/ml, respectively), although the differences were not statistically significant (P = 0.077 and 0.053, respectively). The percentage of IFN-gamma-producing Th cells was significantly higher in normal control subjects than asthmatic patients (23.46 versus 5.72%, P < 0.001) but the percentage of IL-4 producing Th cells did not differ (0.72 versus 0.79%, P > 0.05). Consequently, the Th1/Th2 cell ratio was significantly higher in normal subjects than asthmatic patients (29.6 versus 8.38%, P < 0.001). We propose that allergic asthma is characterized by an elevation of both proinflammatory and Th2 cytokines. The significantly lower ratio of Th1/Th2 cells confirms a predominance of Th2 cells response in allergic asthma.

Fig. 1

Box & whiskers plots of plasma cytokine concentrations of normal controls (n = 30) and allergic asthmatic patients (n = 41): (a) IL-17; (b) IL-6; (c) IL-18; (d) IL-12; (e) IL-10; and (f) IL-13. The differences between normal controls and patients were assessed by Mann–Whitney rank sum tests. *P < 0·05, **P < 0·001.

Fig. 2

Representative dot-plots (PE anti-IL-4 versus FITC anti-IFN-γ) for the analysis of intracellular Th cytokines using FastImmune Cytokine System by flow cytometry: (a) control subject and (b) allergic asthmatic patient. The number in the quadrants denotes the percentage of Th1 and Th2 cells.

Fig. 3

Box & whiskers plot of (a) percentage of IFN-γ producing cells; (b) percentage of IL-4 producing cells; and (c) the ratio of Th1/Th2 cytokine (IFN-γ and IL-4) determined by FastImmune Cytokine System for normal controls (n = 30) and asthmatic patients (n = 41). The differences between controls and patients were assessed by Mann–Whitney rank sum tests. *P < 0·001.