Effects of depletion of cells bearing the interleukin-2 receptor on immunoglobulin production and allergic airway responses in the rat.

Abstract

Lymphocytes, key cells in chronic inflammation, are increased in the airways of asthmatics and have increased expression of the interleukin-2 (IL-2) receptor, a sign of activation. We determined the effects of depleting cells bearing IL-2 receptors on immunoglobulin (Ig) production, airway inflammation, and airway responses after antigen challenge of Brown Norway rats that were sensitized to ovalbumin (OA). Both control and ART-18 (antirat IL-2 receptor) antibodies inhibited plasma specific IgE and the early (ER) and late (LR) airway responses to antigen when given from zero to 14 d after sensitization. When ART-18 was administered from 4 to 14 d after sensitization and compared with control animals, it inhibited OA specific IgE production from Day 21 onward, but it increased total IgE and specific IgG. These changes followed a significant increase in blood CD4+ lymphocytes (%) in ART-18-treated animals 14 d after sensitization. The same protocol of administration did not affect Ig levels at 14 d, but it decreased neutrophil influx into the lungs 8 h after antigen challenge without any effects on the ER and LR. Administration of ART-18 at the time of antigen challenge did not affect the subsequent airway inflammation or the increased responsiveness to methacholine that occurs 32 h after antigen challenge. In summary, depletion of IL-2-receptor-bearing cells affects lymphocyte subsets and immunoglobulin production and it decreases the influx of neutrophils into the lungs 8 h after OA challenge, but it does not significantly inhibit the ER, LR, or increased airway responsiveness after antigen challenge.

Airway neutrophils and interleukin-17

“…For asthma, this is supported by the observation that specific antibodies directed against CD4+ cells inhibit allergen-induced influx of eosinophils and neutrophils into rodent airways in vivo and so do anti-IL-2 receptor antibodies [23,24], whereas it remains to be proven that this is the case in COPD. It is also noteworthy that neutrophils contain defensins that are capable of recruiting and modulating T-lymphocytes [8], thereby providing a possible feedback mechanism between CD4+ cells and neutrophils.…”

“…The interleukin-17 molecule IL-17 is a homodimeric protein comprising 23 amino acids and has a molecular weight ranging 15±22 kDa [24]. Rat (r), mouse (m) and human (h) IL-17 display a high degree of structural homology [24].…”

“…Rat (r), mouse (m) and human (h) IL-17 display a high degree of structural homology [24]. This homology includes the functionally important glycosylation site [24].…”

Neutrophilic airway inflammation and IL‐17

“…It is well known that the total number of lymphocytes as well as eosinophils and neutrophils is increased in the airways of patients with newly diagnosed asthma (52). Furthermore, specific blockade of CD4+ lymphocytes, either with an anti-CD4+ antibody or an anti-IL-2 receptor antibody, prevents allergen-induced recruitment of both eosinophils and neutrophils in sensitized murine airways in vivo (53,54). The number of CD4+ lymphocytes is also increased in parallel with the number of neutrophils in the airways of patients with COPD (55,56) and exposure to cigarette smoke causes recruitment of neutrophils and CD4+ lymphocytes in rodent airways (57).…”

Free, soluble interleukin-17 protein during severe inflammation in human airways

“…As indicated in rodent airways in vivo, the recruitment of neutrophils into the airways can be controlled by activated T-lymphocytes under certain conditions [6][7][8]. Recent studies on rodents in vivo suggest that the cytokine interleukin (IL)-17 links the activation of certain T-lymphocytes to neutrophil recruitment in the airways [1].…”