The expression of activation molecules on peripheral-blood CD4 and CD8 T lymphocytes and the serum concentrations of two products of activated T lymphocytes [interferon-γ (IFN-γ) and soluble interleukin-2 receptor (sIL-2R)] were measured in patients with acute severe asthma (ASA) and controls. Significantly higher percentages of CD4⁺ cells from patients with ASA expressed IL-2R, HLA-DR and VLA-1 as compared to controls (p <0.01). In contrast, CD8⁺ cells from both asthmatics and controls did not express IL-2R and VLA-1, and their expression of HLA-DR in asthmatics was not increased. Serum concentrations of IFN-γ and sIL-2R were significantly elevated in patients with ASA as compared to control groups (p <0.01). Concentrations decreased as the patients improved clinically following therapy. Significant correlations were observed between the improvements in airways obstruction and (1) the decreases in the percentages of peripheral-blood IL-2R⁺ T lymphocytes and (2) the decreases in serum concentrations of sIL-2R. These observations suggest that CD4 T lymphocyte activation is important in the pathogenesis of ASA.

We have compared the effect of inhaled platelet activating factor (PAF) on circulating neutrophils with its ability to induce bronchoconstriction and bronchial hyperresponsiveness in humans. Human volunteers inhaled PAF, given as six successive inhalations 15 min apart, followed by bronchoalveolar lavage (BAL) 4 h later. The mean density and volume of circulating neutrophils were measured by metrizamide gradients and flow cytometry, respectively. PAF caused a decrease in Vp20 of 38.2 +/- 4.5% at 5 min after the first inhalation (p less than 0.001). This was associated with a fall in the peripheral blood neutrophil count from 3.15 +/- 0.3 to 1.1 +/- 0.3 x 10(6) per ml (p less than 0.001), followed by a rebound neutrophilia (p less than 0.01). The mean density of peripheral blood neutrophils fell significantly at 15 min (p less than 0.02), with a return to baseline values despite further PAF inhalations; this was associated with an increase in neutrophil volume (n = 4; p less than 0.05). The numbers of neutrophils (x 10(5] in BAL fluid after PAF were significantly greater than after inhalation of lyso-PAF: 7.1 +/- 1.4 (n = 7) versus 1.3 +/- 0.3 (n = 5, p less than 0.01); eosinophil counts did not change significantly. The PC40 (the concentration of methacholine needed to cause a fall in Vp30) decreased from 17.1 (GSEM 1.40) to 8.7 (1.44) mg/ml (n = 12, p less than 0.02) 3 days after PAF. Inhaled lyso-PAF was inactive in all these respects.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability of cetirizine, a novel antihistamine agent, to inhibit the in vivo activation of human eosinophils, neutrophils and monocytes has been investigated using C3b- and IgG-dependent rosette formation, cytotoxicity against opsonised parasitic larvae and adherence to plasma-coated glass (PCG). The drug inhibited platelet-activating factor (PAF)-induced enhancement of eosinophil and neutrophil IgG (Fc) and complement (C3b) rosettes with an IC₅₀ of 2 × 10^––5M. There was also comparable inhibition of PAF-dependent enhancement of eosinophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Cetirizine inhibited PAF-induced eosinophil, but not neutrophil, hyperadherence to PCG. These data support the view that cetirizine may exert some of its anti-allergic effects by inhibiting the activation of human granulocytes and that it may also selectively inhibit PAF-induced eosinophil hyperadherence.

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