Rhinovirus-mediated changes in airway smooth muscle responsiveness: induced autocrine role of interleukin-1 beta

An important interplay exists between specific viral respiratory pathogens, most commonly rhinovirus (RV), and altered airway responsiveness in the de velopment and exacerbations of asthma. Given that RV infection reportedly i nduces the release of various cytokines in different cell types and that th e reported effects of RV on airway smooth muscle (ASM) responsiveness are h ighly comparable to those obtained in ASM exposed to the proinflammatory cy tokine interleukin (IL)-1 beta, this study examined whether RV (serotype 16 )-mediated pertubations in ASM responsiveness are mechanistically coupled t o altered induced expression and action of IL-1 beta in RV-exposed isolated rabbit and human ASM tissue and cultured cells. Relative to control tissue s, ASM inoculated with RV exhibited significantly increased maximal isometr ic contractility to ACh (P < 0.01) and attenuated relaxation to isoproteren ol (P < 0.005). In extended studies, we found that 1) the RV-induced change s in ASM responsiveness were ablated by pretreating the tissues with the IL -1 recombinant human receptor antagonist; 2) in contrast to their respectiv e controls, RV-inoculated ASM tissue and cultured cells exhibited progressi vely induced expression of IL-1 beta mRNA and elaboration of IL-1 beta prot ein 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 adhesio n molecule-1, the endogenous receptor for most RV. Collectively, these obse rvations provide new evidence demonstrating that "pro-asthmatic-like" pertu bations in agonist responsiveness elicited in RV-exposed ASM are largely at tributed to the induced autologous expression and autocrine action of IL-1 beta in the virus-infected ASM.