Uncontrolled Type-2 inflammation, mediated by IgE , eosinophils and the cytokines IL13 and IL5, is associated with allergic/atopic diseases. Clinical benefit from blocking these factors has been observed in asthma, particularly in patients displaying elevated expression of pathway specific Type-2 biomarkers. Multiple factors, including IL33, regulate expression of these and other pro-inflammatory mediators following lung injury. While perturbation of IL13 or IL5 ameliorates disease in pre-clinical and clinical studies, how each cytokine contributes to individual facets of lung pathology is unclear. We used allergic and infectious models to assess the contribution of IL5 and IL13 on pathways implicated in asthma. Mucus-related pathologies were driven by IL13, while eosinophilia was more sensitive to IL5 activity. To determine whether inflammation could be further reduced by targeting pathways upstream of IL13 or IL5, we compared IL33 inhibition alone or with IL13 or IL5. IL33 obstruction dampened expansion/activation of Type-2 effector cells and granulocyte progenitors, attenuating disease. Simultaneous blockade of IL33 with IL5 or IL13 completely abrogated these pathologies. This highlights the distinct functions of IL5 and IL13, and suggests there is a level of crosstalk between pathways which ultimately manifests in a reduction in overall inflammation upon single cytokine blockade. Moreover, additional therapeutic benefit over single axis therapies may be achievable by combinatorial blockade of IL33 with IL5 or IL13. As many systems can regulate IL5 and IL13, this approach would circumvent this redundancy in addition to obstructing other IL33 regulated inflammatory pathways contributing to disease.