Hemopoietic Processes as Targets of Therapy

While intranasal steroids can improve lower airway hyperresponsiveness, a greater benefit is seen in patients with both allergic rhinitis and asthma if topical steroids are delivered to both sites of inflam-mation. Of less remarkable but still significant clinical benefit, working through a different pathway, montelukast, a specific leukotriene receptor antagonist (LTRA), has been shown to reduce allergic rhinitis and asthma symptoms. Cysteinyl leuko-trienes (CysLTs) are potent receptor agonist mediators capable of inducing cell recruitment and bronchospasm, increased vascular permeability, and nasal airway resistance. Hemopoietic Processes as Targets of Therapy

Table 1—Effects of Several Antiallergic Treatment Options on Hemopoietic Processes and Eosinophils

Treatment Sputum

Eosinophils

Nasal

Eosinophils

Eo/B

Progenitors

Antihistamine Uncertain Reduce/no effect Reduce
LTRA Reduce Reduce Reduce
Topical steroid Reduce Reduce Reduce
Systemic steroid Reduce Reduce Uncertain

Montelukast antagonizes these effects and thus attenuates the allergen-induced early and late asthmatic responses. It also reduces sputum eosinophilia following allergen challenge. Since CysLT receptors are expressed on hemopoietic progenitors, antagonism with montelukast may attenuate tissue eosinophilia via a systemic antiinflammatory effect (see below).

Hemopoietic Processes as Targets of Therapy

Modulation of Eosinophil Differentiation by CS

Hemopoietic mechanisms can be targeted by antiallergic therapies (Table 1). For example, topical treatment with CS can affect the hemopoietic response by abrogation of cytokine production by airways tissues, reduction in peripheral blood Eo/B progenitors, and decreases in BM myeloid progenitors (in a canine asthma model). Most likely, inhaled CS in these models exert their effects on the marrow progenitor response indirectly by interfering with cytokines elaborated from the inflamed tissue, which can then act systemically on the BM. However, a direct effect on progenitors cannot be excluded because there is evidence that, both in vitro and in vivo, low systemic levels of CS (10~9 mol/L) can block differentiation of the Eo/B progenitor in humans and of the myeloid progenitor in dogs.

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