Abstract
BackgroundAsthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods.ResultsFour research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naïve ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-γ ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naïve ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-γ ratio and highest IFN-γ were found.ConclusionIt was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.
Highlights
Asthma is a complicated network of inflammatory reactions
The immunostaining of peripheral blood lymphocytes (PBL) for Bax, Bcl-2, CD4, CD8, CD45RO, and CD45RA The isolated PBL from mild asthmatics, severe asthmatics, and healthy volunteers (HV) groups were examined by immunocytochemistry
It was found that the mean percentage of the positive PBL for Bax was lower in severe asthmatics, 11.48 ± 9.6, than the close figures found in both mild, 29.41 ± 7.4, and HV, 35.23 ± 7.5 (P < 0.05)
Summary
Asthma is a complicated network of inflammatory reactions It is classified into mild, moderate, and severe persistent asthma. The 'Th2 hypothesis for asthma' was first suggested by Mosmann in 1989 [7], who had earlier discovered the presence of two distinct subtypes of helper T cells in mice, namely, T helper 1 (Th1) and T helper 2 (Th2) [8]. These two subclasses of T helper cells differ in their production of cytokines which cross-inhibit each other. A study [12] revealed that some of the Th1-related chemokines were predominant during human allergic pulmonary late-phase reaction
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