Asthma pathogenesis involves activities of other T helper (Th) cells, such as Th17 cells, apart from the known Th1-Th2 cell interaction due to its severity. Pro-inflammatory cytokines, Interleukin (IL)-23/IL-1 \(\beta \) mainly produced by macrophages, are considered essential for differentiating Th17 cells, which mediate neutrophilic inflammation (a major inflammatory characteristic of severe asthma, and resistant to available therapy). Variations in allergen exposure can induce distinct inflammatory phenotypes: an eosinophilic phenotype mediated by Th2 cells, a neutrophilic phenotype mediated by Th17 cells, or a mixed phenotype in severe asthma. We developed a mathematical model describing the regulation of Th2 cells, Th17 cells, and macrophages, incorporating IL-23/IL-1 \(\beta \) cytokines under varying allergen exposure levels to predict potential therapeutic intervention conditions. The model exhibited two steady-state scenarios corresponding to the absence and presence of allergen, characterized by a transcritical forward bifurcation and mono-, bi-stability with hysteresis reflecting asthma severity, respectively. Bifurcation analysis predicted that the secretion rate of IL-23/IL-1 \(\beta \) cytokines, together with the leaving rate of macrophages, are significant factors influencing neutrophilic inflammation. These findings suggest that modulating these parameters may offer effective therapeutic strategies to control asthma severity and shift the system further towards a healthier outcome.
