Altered intracellular expression of the chemokines MIP‐1α, MIP‐1β and IL‐8 by peripheral blood CD4⁺ and CD8⁺ T cells in mild allergic asthma

Abstract

Background: The ability of chemokines to regulate Th1 and Th2 responses suggests a role in the pathogenesis of atopic disorders such as allergic asthma where Th2 response dominance has been observed. Although the impact of allergic asthma on local chemokine production in the lung has been the subject of investigation, little is know about the influence of disease progression on peripheral chemokine production. We now report use of whole blood culture and flow cytometry to assess the influence of mild allergic asthma on peripheral T‐cell chemokine expression. Methods: Study participants included patients with mild allergic asthma (n = 7) and nonasthmatic controls (n = 7). Following in vitro stimulation of peripheral venous blood with phorbol 12‐myristate acetate (PMA) and ionomycin, flow cytometry was used to estimate the percentage of CD4+ and CD8+ T cells producing a number of chemokines, including macrophage inflammatory proteins MIP‐1α and MIP‐1β, RANTES (regulated on activation, T‐cell expressed and secreted), monocytic chemotactic protein‐1 (MCP)‐1, and interleukin (IL)‐8, or the cytokines interferon (IFN)‐γ and IL‐4. Serum levels of MIP‐1α, MIP‐1β, RANTES, MCP‐1, IL‐8, IFN‐γ and IL‐4 were also assessed by quantitative ELISA. Results: Intracellular expression of MIP‐1β by CD4+ and CD8+ T cells from allergic asthmatics was significantly reduced in comparison to that observed for nonasthmatics (median = 2.29% (1.75–3.50) vs 4.57% (3.38–6.64), P = 0.05; 14.20% (13.18–17.88) vs 44.10% (30.38–48.70), P = 0.01). Similarly, intracellular expression of MIP‐1α by CD8+ T cells from allergic asthmatics was also significantly lower (3.67% (1.17–5.42) vs 17.10% (4.97–20.43), P = 0.05). Conversely, IL‐8 expression by both CD4+ and CD8+ T cells from allergic asthmatics demonstrated significant enhancement (9.93% (7.77–11.28) vs 4.14% (3.61–7.11), P = 0.05; 8.40% (6.97–10.04) vs 4.98% (3.37–6.08), P = 0.05). Examination of intracellular IFN‐γ and IL‐4 revealed no significant difference in the expression of either cytokine by CD4+ T‐cells from allergic asthmatics and nonasthmatics. In contrast, expression of IFN‐γ was significantly reduced in CD8+ T‐cells from allergic asthmatics (24.60% (21.08–32.50) vs 48.40% (41.50–55.28), P = 0.01). Conclusions: The occurrence in mild allergic asthma of peripheral T‐cell chemokine expression suggestive of a diminished Th1 response, coinciding with marginal change in cytokine profiles indicative of a Th2 response bias, confirms the importance of chemokine involvement in the etiology of allergic asthma. The ability to use whole blood culture to estimate chemokine expression in T cell subsets may ultimately provide a practical means to evaluate disease status and to monitor early intervention therapies which target chemokines.

CCL4 Levels Differ between Aspirin-Tolerant and Aspirin-Intolerant Patients with Asthma

“…Diminished CCL4 production by CD4+ and CD8+ T cells in patients with allergic asthma has been reported by Grob et al [18]. Despite that there was no correlation between cellular and serum levels of CCL4, the authors elucidated polarization away from the Th1 response, along with a Th2-response bias in patients with ATA.…”

Useful biomarkers for assessing the adverse health effects of PCBs in allergic children: pediatric molecular epidemiology

“…Study 1: IL-8, a chemokine associated with inflammation, has been reported to be linked to childhood allergies, particularly those involving inflammation of the airways, which can result in wheezing or asthma [26][27][28]. As for the use of IL-8 as a biomarker, IL-8 has already been suggested to be a marker of asthma and/or other inflammatory lung conditions such as chronic obstructive pulmonary disease by a number of other scientists [29,30]. Nevertheless, despite the wealth of information about the relationship between IL-8 and asthma, no one has investigated whether IL-8 is a useful biomarker for examining the link between PCB exposure and childhood asthma.…”

Correlation between peripheral blood T-cell profiles and airway inflammation in atopic asthma

“…11 Whether IL-4-or IFN-g-producing CD8 1 T cells from peripheral blood are predominant in asthma is also controversial. 9,10,12,13 Recent studies have investigated cytokine production in bronchoalveolar lavage fluid or induced sputum T cells, raising the possibility that pulmonary T-lymphocyte profiles might be different from those of peripheral blood, and a consensus has not been established either. 10,14,15 Very few studies have assessed the relationship between T-cell profiles and airway hyperresponsiveness or atopic status of asthma.…”