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Divisions of 1 Pulmonary Medicine and 2 Immunologic and Infectious Diseases, Joseph Stokes, Jr. Research Institute, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
An important interplay exists between specific
viral respiratory pathogens, most commonly rhinovirus (RV), and altered
airway responsiveness in the development and exacerbations of asthma. Given that RV infection reportedly induces the release of various cytokines in different cell types and that the reported effects of RV
on airway smooth muscle (ASM) responsiveness are highly comparable to
those obtained in ASM exposed to the proinflammatory cytokine
interleukin (IL)-1
, this study examined whether RV (serotype 16)-mediated pertubations in ASM responsiveness are mechanistically coupled to altered induced expression and action of IL-1 in
RV-exposed isolated rabbit and human ASM tissue and cultured cells.
Relative to control tissues, ASM inoculated with RV exhibited
significantly increased maximal isometric contractility to ACh
(P < 0.01) and attenuated relaxation
to isoproterenol (P < 0.005). In
extended studies, we found that 1)
the RV-induced changes in ASM responsiveness were ablated by
pretreating the tissues with the IL-1 recombinant human receptor
antagonist; 2) in contrast to their
respective controls, RV-inoculated ASM tissue and cultured cells
exhibited progressively induced expression of IL-1 mRNA and
elaboration of IL-1 protein at 6 and 24 h after viral exposure; and
3) the latter effect of RV was
inhibited in the presence of a monoclonal antibody to intercellular
adhesion molecule-1, the endogenous receptor for most RV. Collectively,
these observations provide new evidence demonstrating that
"pro-asthmatic-like" pertubations in agonist responsiveness
elicited in RV-exposed ASM are largely attributed to the induced
autologous expression and autocrine action of IL-1 in the
virus-infected ASM.
cholinergic contractility; -adrenoceptor relaxation; viral
respiratory infection; cytokine signaling; airway reactivity; asthma
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