IL-4-independent pathways exacerbate methacholine-induced airway hyperreactivity during mycoplasma respiratory disease

Mycoplasma respiratory infections are associated with wheezing and exacerbation of airway hyperresponsiveness (AHR) in asthmatic patients. IL-4 is a key cytokine in the development of AHR and airway reconstruction in asthmatic patients and might be an important component in exacerbation of AHR during pulmonary mycoplasma infection.This study evaluates the effect of IL-4 on the severity of methacholine-induced AHR associated with mycoplasma pulmonary mycoplasma infection.BALB/c and IL-4 knockout (KO) mice were infected with Mycoplasma pulmonis, and their enhanced pause scores were monitored before and after methacholine inhalation with whole-body plethysmography.IL-4 KO mice showed no difference in histopathology of the lungs before or after Mycoplasma pulmonis infection when compared with BALB/c mice. There was an increase in airway obstruction from days 7 to 21 after infection in both strains of mice, but there was no strain difference in airway resistance-associated mycoplasma disease. However, IL-4 KO mice had significantly higher methacholine-induced AHR after M pulmonis infection when compared with BALB/c mice. There was no difference in AHR between uninfected IL-4 KO and control mice.In contrast to our hypothesis, IL-4-independent pathways exacerbate methacholine-induced AHR and promote airway obstruction during the pathogenesis of mycoplasma respiratory disease.