Evidence for a Th2-to-Th1 shift in IL-4 deficient mice in response to chronic house dust mite exposure

RationaleIL-4 is an important mediator in the development of Th2-type inflammation in the airway. We therefore examined the response of IL-4 deficient (4KO) mice to chronic house dust mite (HDM) exposure, a protocol that results in a Th2-skewed response in wild type (WT) mice.MethodsHDM was administered intranasally for five consecutive weeks. After full resolution of this inflammatory response, mice were rechallenged on five consecutive days with HDM. Lung inflammation, in vitro cytokine production, serum immunoglobulins and lung cell phenotype were assessed.ResultsBoth WT and 4KO mice mounted an airway inflammatory response after 5 weeks of HDM exposure. However, the degree of inflammation was significantly greater in WT mice. Upon in vivo recall, both WT and 4KO mice mounted a robust inflammatory response of similar magnitude. At these two time points, inflammation in 4KO mice was comprised of macrophages and lymphocytes and, in contrast to WT mice, a near complete absence of eosinophils. Splenocytes from both strains produced similar levels of IFN-γ; however, splenocytes from 4KO mice produced minimal amounts of IL-5 and IL-13 upon HDM recall. In addition, 4KO mice had markedly reduced numbers of CD3+/CD4+ lung cells expressing IL-5 and T1/ST2. In serum, we observed increased levels of IgG1 and modest levels of IgG2 in WT mice, and the reverse profile in 4KO mice.ConclusionsThe genetic deletion of IL-4 does not impede the generation of airway inflammation in response to chronic HDM exposure. However, the absence of IL-4 facilitates the generation of a Th1-polarized immune-inflammatory response.